RARRES1 inhibits hepatocellular carcinoma progression and increases its sensitivity to lenvatinib through interaction with SPINK2.

BACKGROUND: Lenvatinib is an oral small molecule inhibitor approved for treating patients with unresectable hepatocellular carcinoma (HCC) worldwide. Increasing cell sensitivity to lenvatinib would be an effective method of improving therapeutic efficacy. METHODS: High throughput methods was used to scan the differentially expressed genes (DEGs) related to lenvatinib sensitivity in HCC cells. Gain- and loss-function experiments were used to explore the functions of these DEGs in HCC and lenvatinib sensitivity. CO-IP assay and rescue experiments were utilized to investigate the mechanism. RESULTS: We identified that RAR responder protein 1 (RARRES1), a podocyte-specific growth arrest gene, was among significantly upregulated DEGs in HCC cells following lenvatinib treatment. Functional analysis showed that ectopic RARRES1 expression decreased HCC progression in vitro and in vivo, as well as improving tumor sensitivity to lenvatinib, while RARRES1 silencing increased HCC cell proliferation and migration. Mechanistically, co-immunoprecipitation assays demonstrated that RARRES1 interacted with serine protease inhibitor Kazal-type 2 (SPINK2) in HCC cells. Further, SPINK2 overexpression suppressed HCC cell proliferation and migration, as well as increasing sensitivity to lenvatinib whereas SPINK2 knockdown promoted cell progression and decreased lenvatinib sensitivity. The mRNA and protein levels of RARRES1 and SPINK2 were low in HCC tissue samples, relative to those in normal liver tissue. CONCLUSIONS: Our findings highlighted that RARRES1 can inhibit HCC progression and regulate HCC sensitivity to lenvatinib by interacting SPINK2, representing a new tumor suppressor RARRES1/SPINK2 axis in HCC that modulates sensitivity to lenvatinib.

The association between serum orexin-A levels and sleep quality in pregnant women.

OBJECTIVE/BACKGROUND: Orexin has been shown to regulate the sleep-wake cycle, and it may play a major role in the pathogenesis of sleep disorders; however, its role in sleep disorders in pregnant women remains unclear. We aimed to assess the relationship between serum orexin-A (OXA) levels and sleep quality in pregnant women. PATIENTS/METHODS: This study comprised 214 enrolled pregnant women (poor sleep quality, n = 125; no poor sleep quality, n = 89). We assessed participants' sleep quality and depression and anxiety levels. OXA levels were measured using enzyme-linked immunosorbent assay. RESULTS: Women in the poor sleep quality group showed higher serum OXA levels (0.33[0.3] vs. 0.27[0.11], P < 0.001) than those in the no poor sleep quality group. Binary regression analysis showed that the higher the OXA levels (odds ratio [OR] 1.385, 95% CI [confidence interval] 1.160-1.655) and Zung Self-Rating Anxiety Scale scores (OR 1.073, 95% CI 1.009-1.140), the greater the risk of sleep quality in pregnant women. First-trimester OXA levels differed significantly from those in the second and third trimesters (P < 0.05). CONCLUSION: Serum OXA levels were higher in pregnant women with poor sleep quality than in those without poor sleep quality. OXA levels were also higher in the second and third trimesters than in the first trimester.

Effects of spore powder of ganoderma lucidum on CaSR and apoptosis-related proteins in hippocampus tissue of epilepsy following dementia: A protocol of systematic review.

BACKGROUND: This study will investigate the effects of Spore Powder of Ganoderma Lucidum (SPGL) on CaSR and apoptosis-related proteins (ARP) in hippocampus tissue of epilepsy following dementia. METHODS: This study will retrieve all potential studies from both electronic databases (Cochrane Library, EMBASE, MEDLINE, CINAHL, AMED, and CNKI) and other literature sources to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. We will search all literature sources from the inception to the present. All eligible case-control studies will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality evaluation. Any divergence will be resolved by another author through discussion. RevMan 5.3 software will be employed for data analysis. RESULTS: This study will summarize existing evidence to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. CONCLUSIONS: The findings of this study may provide helpful evidence of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070041.

Impact of early diagnosis of carotid artery stenosis by carotid ultrasound: A protocol of systematic review and meta-analysis.

BACKGROUND: The purpose of this study is to explore the impact of carotid ultrasound (CU) for early diagnosis of carotid artery stenosis (CAS). METHODS: Literatures will be sought from the following electronic databases: MEDLINE, EMBASE, Cochrane Library, PSYCINFO, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure. The search will cover from the start of indexing to the present without any limitations of language and publication status. All study quality will be assessed by Quality Assessment of Diagnostic Accuracy Studies tool, and data will be analyzed by RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will investigate the impact of CU for early diagnosis of CAS through sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. CONCLUSION: The findings of this study may provide helpful evidence for the impact of CU for early diagnosis of CAS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153904.

Can cervical vascular ultrasound combined with transcranial Doppler ultrasound accurately diagnose cerebral infarction?: A protocol for a systematic review and meta-analysis.

BACKGROUND: The purpose of this study is to investigate the impact of cervical vascular ultrasound (CVU) combined transcranial Doppler ultrasound (TDU) in the diagnosis of cerebral infarction (CI). METHODS: The following electronic databases will be sought from PUBMED, EMBASE, Cochrane Library, PSYCINFO, Web of Science, Allied and Complementary Medicine Database, WANGFANG, VIP database, and China National Knowledge Infrastructure. The search period will cover from the initial indexing to March 1, 2020 without restrictions of language and publication status. All case-controlled studies which identifying the impact of CVU combined TDU in the diagnosis of CI will be considered. Two authors will independently perform the whole process of study selection, data extraction, and quality assessment, respectively. If any disagreements occur between two authors, we will invite a third experienced author to help solve them through discussion. Quality Assessment of Diagnostic Accuracy Studies tool will be used to check study quality, and RevMan V.5.3 software and Stata V.12.0 software will be utilized to carry out statistical analysis. RESULTS: This study will summarize the most recent evidence that focusing on the impact of CVU combined TDU in the diagnosis of CI. CONCLUSION: This study will provide helpful evidence to determine whether CVU combined TDU is an accurate diagnosis tool for CI or not. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020171367.

Reciprocal modulation of 5-HT and octopamine regulates pumping via feedforward and feedback circuits in C. elegans.

Feeding is vital for animal survival and is tightly regulated by the endocrine and nervous systems. To study the mechanisms of humoral regulation of feeding behavior, we investigated serotonin (5-HT) and octopamine (OA) signaling in Caenorhabditis elegans, which uses pharyngeal pumping to ingest bacteria into the gut. We reveal that a cross-modulation mechanism between 5-HT and OA, which convey feeding and fasting signals, respectively, mainly functions in regulating the pumping and secretion of both neuromodulators via ADF/RIC/SIA feedforward neurocircuit (consisting of ADF, RIC, and SIA neurons) and ADF/RIC/AWB/ADF feedback neurocircuit (consisting of ADF, RIC, AWB, and ADF neurons) under conditions of food supply and food deprivation, respectively. Food supply stimulates food-sensing ADFs to release more 5-HT, which augments pumping via inhibiting OA secretion by RIC interneurons and, thus, alleviates pumping suppression by OA-activated SIA interneurons/motoneurons. In contrast, nutrient deprivation stimulates RICs to secrete OA, which suppresses pumping via activating SIAs and maintains basal pumping and 5-HT production activity through excitation of ADFs relayed by AWB sensory neurons. Notably, the feedforward and feedback circuits employ distinct modalities of neurosignal integration, namely, disinhibition and disexcitation, respectively.

Spore powder of Ganoderma lucidum for Alzheimer's disease: A protocol for systematic review.

BACKGROUND: Previous studies have reported that spore powder of Ganoderma lucidum (SPGL) may be effective for the treatment of Alzheimer's disease (AD). However, its efficacy is still inconclusive. Thus, this systematic review will aim to assess its efficacy and safety for AD. METHODS: We will search the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database to assess the efficacy and safety of SPGL for patients with AD from their inceptions to the present. All case-control studies and randomized controlled trials will be considered for inclusion in this study. Two review authors will independently perform the study selection, data extraction, and risk of bias evaluation. RESULTS: The primary outcome includes the cognitive status for patients. The secondary outcomes consist of the quality of life, AD symptoms, and adverse events. CONCLUSIONS: This systematic review will present the existing evidence for the efficacy and safety of SPGL for treating patients with AD. DISSEMINATION AND ETHICS: The results of this systematic review will be disseminated by through peer-reviewed journals. It does not needs ethic approval, because it does not involve individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019119426.

cGMP Signalling Mediates Water Sensation (Hydrosensation) and Hydrotaxis in Caenorhabditis elegans.

Animals have developed the ability to sense the water content in their habitats, including hygrosensation (sensing humidity in the air) and hydrosensation (sensing the water content in other microenvironments), and they display preferences for specific water contents that influence their mating, reproduction and geographic distribution. We developed and employed four quantitative behavioural test paradigms to investigate the molecular and cellular mechanisms underlying sensing the water content in an agar substrate (hydrosensation) and hydrotaxis in Caenorhabditis elegans. By combining a reverse genetic screen with genetic manipulation, optogenetic neuronal manipulation and in vivo Ca(2+) imaging, we demonstrate that adult worms avoid the wetter areas of agar plates and hypo-osmotic water droplets. We found that the cGMP signalling pathway in ciliated sensory neurons is involved in hydrosensation and hydrotaxis in Caenorhabditis elegans.

Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in Caenorhabditis elegans.

The off-response of ASH neurons had been overlooked until the microfluidic devices were introduced for in vivo imaging of neuronal activity in Caenorhabditis elegans. The mechanisms of ASH off-response were completely unknown. Here we monitored ASH off-response to CuSO4 stimulation by use of microfluidic device and genetically encoded calcium indicator (GECI) - Case12. We found ASH neurons exhibited a multiphasic response to 10 mM and 50 mM CuSO4 of 30-s stimulation duration. ASH off-responding to Cu(2+) had been dramatically reduced in goa-1, mod-5, trpa-1 and egl-8 mutants. Moreover, in osm-9 mutants ASH off-response was completely eliminated. Neuron-specific rescue of osm-9 in ASH neurons restored the off-response and the normal avoidance behavior in worms.

[Maturation regulation of dendritic cells pulsed with hepatocellular carcinoma cell soluble antigens].

OBJECTIVE: To research the maturation regulation of dendritic cells (DCs) pulsed with hepatocellular carcinoma (HCC) cell soluble antigens. METHODS: BCG HSP 70 was purified by SDS-PAGE electrophoresis and its biological activity was determined with ELISA. Phenotypes of DCs pulsed with antigens or with both antigens and BCG HSP 70 were analysed with flow cytometry. MTT assay was used to estimate the proliferation of self lymphocytes and the mixed lymphocyte reaction (MLR) of BCG HSP 70 primed DCs. RESULTS: The characteristics of DCs had changed after loaded with soluble antigens of HCC. There were about 10% DCs which had lost their specific markers. The expression levels of CD54, CD83, CD86 molecules and the stimulatory ability in allogeneic MLR decreased. However, after being activated by BCG HSP 70, the DCs pulsed with antigens could keep their special markers and the expression levels of CD54, CD83, CD86 molecules increased too. The stimulatory abilities in allogeneic MLR and proliferation of self lymphocytes also improved. CONCLUSION: This study shows that BCG HSP 70 can induce DCs pulsed with antigens maturation and improve their antigen-presenting ability, which may be a useful maturation inducer for dendritic cells.

[Immune responses of dendritic cells after loaded with cytotoxicity T lymphocyte epitope based peptide of human alpha-fetoprotein (hAFP)].

OBJECTIVE: To study the immune responses of lymphocytes after activated by dendritic cells (DCs) loaded with cytotoxicity T lymphocyte (CTL) epitope based peptide of human alpha-fetoprotein (hAFP, 218-226 LLNQHACAV). METHODS: Get high purity DCs by cultured plastic-adherent monocytes isolated from healthy donor of HLA-A2(+) peripheral blood with granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days. Stimulate self-lymphocytes with DCs that loaded with CTL epitope based peptide of hAFP under the culture medium contains interleukin-2 (IL-2) for 7 days. Analyse IL-12 and TNF in culture medium and also the specific lysis activity of lymphocytes against four strains of primary hepatocellular carcinoma cells. RESULTS: After stimulated by DC loaded with CTL epitope based peptide derived from hAFP, lymphocytes appeared a good characteristics and the culture medium of activated lymphocytes contained a high level Th1 type cytokines of IL-12 and TNF. Activated lymphocytes not only specifically lysed HLA-A2(+) HepG2 line but also had the cytotoxicity against other three primary hepatocellular carcinoma cell lines and T2 target cell loaded with peptide of hAFP. CONCLUSIONS: The results of this research supply the basic materials for the DC based vaccine with HLA-A2 restricted peptide epitope derived from hAFP against AFP positive primary hepatocellular carcinoma.