Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

TRIM44 Promotes Endometrial Carcinoma Progression by Activating the FRS2 Signalling Pathway.

The Tripartite Motif Containing 44 (TRIM44) is highly expressed in a variety of tumours. However, the TRIM44's role in endometrial carcinoma (EC) progression remains unknown. To investigate the TRIM44's role in the development and metastasis of EC, we detected TRIM44 expression in EC cell lines and surgical specimens from patients with EC using immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and western blotting analysis. The biological functions of TRIM44 by loss-of-function analysis in RL95-2 and Ishikawa cells were studied. The effect of TRIM44 on the progression of EC in terms of cell proliferation, apoptosis, and invasion was examined and revealed its underlying mechanism in vitro using EC cell lines and in vivo using mouse xenograft models. The TRIM44's expression was positively correlated with EC progression and poor prognosis. The TRIM44 knockdown reduced the EC cell proliferation and invasion while promoting cell apoptosis. Mechanism experiments showed that the TRIM44 interacts with Fibroblast Growth Factor Receptor Substrate 2 (FRS2) and negatively regulates the expression of Bone Morphogenetic Protein 4(BMP4), ß-catenin, and Transforming Growth Factor Beta Receptor 1(TGF-ßR1). Moreover, the effect of TRIM44 overexpression on EC cell proliferation, invasion, and apoptosis is reversed by the FRS2 knockdown. Our study may provide a new perspective on targeting the TRIM44/FRS2 signaling pathway in treating EC, which deserves further investigation.

Efficacy and safety of manual acupuncture for the treatment of upper limb motor dysfunction after stroke: Protocol for a systematic review and meta-analysis.

INTRODUCTION: The incidence of stroke sequelae among patients is as high as 70%-80%. Flexor spasm is the most common stroke sequela, presenting a heavy burden to the patients and their families. This study will evaluate the results of randomized controlled trials to determine the efficacy and safety of hand manipulation acupuncture for the treatment of upper limb motor dysfunction after stroke. METHODS: Eight databases, including China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PubMed, Wanfang Database, and Web of Science, will be searched using English and Chinese search strategies. In addition, manual retrieval of research papers, conference papers, ongoing experiments, and internal reports, among others, will supplement electronic retrieval. All eligible studies published on or before January 15, 2021 will be selected. To enhance the effectiveness of the study, only clinical randomized controlled trials related to the use of manual acupuncture for the treatment of upper limb motor dysfunction after stroke will be included. ANALYSIS: The Fugl-Meyer upper extremity assessment will be the primary outcome measure, whereas the Wolf Motor Function Test, Modified Ashworth Scale, arm movement survey test table, and upper extremity freehand muscle strength assessment scores will be the secondary outcomes. Side effects and adverse events will be included as safety evaluations. To ensure the quality of the systematic evaluation, study selection, data extraction, and quality assessment will be independently performed by two authors, and a third author will resolve any disagreement. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of manual acupuncture for the treatment of upper limb motor dysfunction after stroke. Since all included data will be obtained from published articles, it does not require ethical approval and will be published in a peer-reviewed journal. INPLASY registration number: INPLASY202110071.

Use of Cardiovascular Drugs for Primary and Secondary Prevention of Cardiovascular Disease Among Rural-Dwelling Older Chinese Adults.

Cardiovascular risk factors and related disorders are common among older adults, and use of various classes of cardiovascular (CV) drugs could reduce the risk of cardiovascular disease (CVD). However, data are sparse with regard to the use of CV drugs among rural-dwelling older adults in China. Therefore, this population-based study aimed to describe use of CV drugs among older adults living in the rural communities in China, while taking into account the use of CV drugs for primary and secondary prevention of CVDs. This study included 5,246 participants (age ≥65 years; 57.17% women; 40.68% illiteracy) in the baseline examination of the MIND-China study. In March-September 2018, data on health-related factors, CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), and CV drug use were collected via face-to-face survey, clinical examination, and laboratory tests. We classified CV drugs according to the Anatomical Therapeutic Chemical classification system for western medications and specific cardiovascular effects for the products of traditional Chinese medicine (TCM). We conducted descriptive analysis. The overall prevalence of major cardiovascular risk factors ranged from 14.30% in diabetes and 23.81% in dyslipidemia to 66.70% in hypertension, and CVDs affected 35.07% of all participants (36.28% in women vs. 33.47% in men, p = 0.035). In the total sample, calcium channel blockers (C08) were most commonly used (10.39%), followed by TCM products (7.64%), hypoglycemic agents (A10, 4.73%), renin-angiotensin system (RAS)-acting agents (C09, 4.61%), and lipid-lowering agents (C10, 4.17%). The proportions of CV drugs for primary prevention (i.e., use of CV drugs among people without CVD) were 3.14% for antithrombotic agents (mainly aspirin), 1.38% for lipid-lowering agents, and 3.11% for RAS-acting agents; the corresponding figures for secondary prevention (i.e., use of CV drugs among people with CVD) were 13.97%, 9.35%, and 7.39%. In conclusion, despite highly prevalent cardiovascular risk factors and CVDs, a fairly low proportion of the rural-dwelling older adults take CV medications for primary and secondary prevention. Notably, TCM products are among the most commonly used CV drugs. These results call for additional efforts to promote implementation of the evidence-based recommendations for prevention of CVDs in the primary care settings.

Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons.

Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

Screening of the anti-tumor active fraction from Ipomoea batatas Lam. (cv.simon) leaves / 中南大学学报(医学版)

OBJECTIVE@#Three fractions (SM, SM-A, SM-B) were prepared from different polarity parts of Ipomoea batatas Lam. (cv.simon) leaves and the anti-tumor potency as well as the dose-response relations were evaluated.@*METHODS@#The anti-tumor activities of fraction SM, SM-A or SM-B were screened by MTS in human hepatic cancer Hep3B cells, lung cancer A549 cells or gastric carcinoma MGC803 cells, respectively.@*RESULTS@#The three fractions all showed anti-tumor activities in three cancer cells with different sensitivity. Among them, SM-B was the most potent fraction with IC50 values at 15.17 mg/L, 72.64 mg/L or 165.47 mg/L in MGC803 cells, A549 cells or Hep3B cells, respectively (P<0.05).@*CONCLUSION@#Th e extraction of Brazil sweet potato leaves displayed anti-tumor activity and SM-B was the most potent fraction.

Lipid emulsions in parenteral nutrition: current applications and future developments.

INTRODUCTION: A parenteral lipid emulsion (LE), used as a key source of energy, essential fatty acids (FAs), and fat-soluble vitamins, is an integral part of a parenteral nutrition (PN) regimen. The conventional LEs, such as soybean oil (SO)-based emulsions, have caused concerns about the potential adverse effects involving oxidative stress, inflammation, and immune response probably because of undesirable FA composition. AREAS COVERED: Recently, alternative LEs, optimizing the FA composition with partial substitution of SO with medium-chain triglyceride (MCT), olive oil (OO), and fish oil (FO), have been developed and applied in clinical practice. This review summarizes the characteristics and beneficial clinical effects of alternative parenteral LEs in critically ill, pediatric, and long-term PN patients. EXPERT OPINION: More clinical data from sufficiently high-powered studies are required to characterize the integral biological properties of alternative LEs for further selection to fit individual needs and disease characteristics. Simultaneously, potential lipid sources with desirable FA compositions and biological properties should be selected to develop new therapeutic LEs. As supplements to current parenteral lipids, the new LEs with different therapeutic effects are expected to fit specified subpopulations of patients with different diseases. Great efforts should be devoted to the development of parenteral LEs.

Cloning and expression analysis of SKn-type dehydrin gene from bean in response to heavy metals.

A heavy metal responsive gene PvSR3 (GenBank accession number U54703) encoding an acid dehydrin was isolated from a mercuric chloride-treated bean (Phaseolus vulgaris L.) leaf cDNA library by differential screening using cDNAs derived from treated and untreated plants. The PvSR3 cDNA is 981-bp long and has a 606-bp open-reading frame with a 202-residue-deduced amino acid sequence. The PvSR3 sequence contains two conserved repeats of the characteristic lysine-rich K segment (EKKGIMDKIKEKLPG) preceded by an 8-serine residue stretch, whereas the Y segment (DEYGNP) conserved motif is absent. The deduced protein has a calculated molecular weight of 23 kDa and an isoelectric point of 5.2. Sequence similarity and comparative analysis showed that PvSR3 shares 70 and 73% similarity with the dehydrin of poplar and pepper, respectively. Southern hybridizations indicated that PvSR3 was a low copy-number gene. Northern blot analysis revealed that PvSR3 mRNA was weakly detected in seedling leaves. However, the gene expression was strongly stimulated by heavy metals, such as mercury, cadmium, arsenic, and copper, whereas virus infection and salt had little effect on it. In contrast, PvSR3 was not responsive to drought or abscisic acid (ABA), and was downregulated by UV radiation. Furthermore, PvSR3 was upregulated by the exogenous signaling molecules, including salicylic acid (SA) and hydrogen peroxide (H2O2). It is suggested that PvSR3 is extremely related to heavy metal stress, and might play an important role in metal detoxification and resistance to the damage caused by heavy metals.

Xenopus laevis is a potential alternative model animal species to study reproductive toxicity of phytoestrogens.

This study investigated effects of phytoestrogen quercetin on the gonadal development in Xenopus laevis. X. laevis at Nieuwkoop and Faber stage 46/47 were exposed to 50, 100 and 200 microg/L quercetin till 1 month postmetamorphosis. Gonads from frogs at 1 and 3 months postmetamorphosis were examined in gross morphology and histology. The highest dose of quercetin as well as estradiol (E2) significantly increased the percentages of phenotypic females. Exposure to quercetin at all doses induced abnormal testes with certain ovarian characteristics to some degree in gross morphology, including ovotestes. The abnormality rate exceeded 10% in each quercetin treatment. Histologic examination revealed that some abnormal testes exhibited intersexuality with testicular structure and ovarian structure or oocytes interspersed in testicular structure at 1 month postmetamorphosis. At 3 months postmetamorphosis, testicular abnormalities were more obvious, such as necrosis or apoptosis of spermatogonia, occurrence of developed or undeveloped oocytes, delay of the development of seminiferous tubes without or less late stage spermatocytes. The results have shown that quercetin cannot only feminize but also impair testicular development of X. laevis, i.e. X. laevis is sensitive to phytoestrogen. It is suggested that X. laevis might be an alternative model species to study reproductive toxicity of phytoestrogens.