The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers.

Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly.

Mitochondrial deoxyguanosine kinase is required for female fertility in mice.

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome.

Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4 T cells.

The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4 T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4 T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation.

Drosophila transition fibers are essential for IFT-dependent ciliary elongation but not basal body docking and ciliary budding.

Cilia are highly conserved organelles critical for animal development and perception. Dysfunction of cilia has been linked to a wide spectrum of human genetic diseases, termed ciliopathies. Transition fibers (TFs) are striking ciliary base structures essential for cilia assembly.

DYF-4 regulates patched-related/DAF-6-mediated sensory compartment formation in C. elegans.

Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans, we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension.

CEP290 is essential for the initiation of ciliary transition zone assembly.

Cilia play critical roles during embryonic development and adult homeostasis. Dysfunction of cilia leads to various human genetic diseases, including many caused by defects in transition zones (TZs), the "gates" of cilia. The evolutionarily conserved TZ component centrosomal protein 290 (CEP290) is the most frequently mutated human ciliopathy gene, but its roles in ciliogenesis are not completely understood.

Structures/cytotoxicity/selectivity relationship of natural steroidal saponins against GSCs and primary mechanism of tribulosaponin A.

Glioblastoma multiform (GBM) is the highly aggressive brain tumor with poor prognosis. Glioma stem cells (GSCs), small population of cancer cells that exist in GBM tissues, resistant to chemotherapy and radiotherapy and usually driving GBM recurrence, have been developed as effective therapeutic target. Steroidal saponins are one of important resources for anti-tumor agent and may be benefited to selectively clear GSCs.

Neothalfine, a potent natural anti-tumor agent against metastatic colorectal cancer and its primary mechanism.

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC values of 7.2, 5.

Pharmacological Inhibition of PPARy Boosts HIV Reactivation and Th17 Effector Functions, While Preventing Progeny Virion Release and de Infection.

The frequency and functions of Th17-polarized CCR6RORytCD4 T cells are rapidly compromised upon HIV infection and are not restored with long-term viral suppressive antiretroviral therapy (ART). In line with this, Th17 cells represent selective HIV-1 infection targets mainly at mucosal sites, with long-lived Th17 subsets carrying replication-competent HIV-DNA during ART. Therefore, novel Th17-specific therapeutic interventions are needed as a supplement of ART to reach the goal of HIV remission/cure.

Functional Analysis of Hydrolethalus Syndrome Protein HYLS1 in Ciliogenesis and Spermatogenesis in .

Cilia and flagella are conserved subcellular organelles, which arise from centrioles and play critical roles in development and reproduction of eukaryotes. Dysfunction of cilia leads to life-threatening ciliopathies. HYLS1 is an evolutionarily conserved centriole protein, which is critical for ciliogenesis, and its mutation causes ciliopathy-hydrolethalus syndrome.

Improving HIV Outgrowth by Optimizing Cell-Culture Conditions and Supplementing With Retinoic Acid.

The persistence of replication-competent HIV reservoirs in people living with HIV (PLWH) receiving antiretroviral therapy (ART) is a barrier to cure. Therefore, their accurate quantification is essential for evaluating the efficacy of new therapeutic interventions and orienting the decision to interrupt ART. Quantitative viral outgrowth assays (QVOAs) represent the "" for measuring the size of replication-competent HIV reservoirs.

TALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating.

Transition fibers (TFs) regulate cilia gating and make the primary cilium a distinct functional entity. However, molecular insights into the biogenesis of a functional cilia gate remain elusive. In a forward genetic screen in Caenorhabditis elegans, we uncover that TALP-3, a homolog of the Joubert syndrome protein TALPID3, is a TF-associated component.

Whole genome sequence analysis of the mosquitocidal Bacillus thuringiensis LLP29.

Bacillus thuringiensis (Bt) is efficient, strongly specific, and avirulent to humans, making it one of the most popular biopesticides in the world. Bt LLP29 is a mosquitocidal strain that was first isolated from Magnolia denudata. To understand its molecular mechanism against mosquitoes, the genome of Bt LLP29 was sequenced and annotated in this study.

Everolimus inhibits the proliferation and migration of epidermal growth factor receptor-resistant lung cancer cells A549 via regulating the microRNA-4328/phosphatase and tensin homolog signaling pathway.

Lung cancer is the most common cancer type worldwide, and investigating novel therapeutics methods for the treatment of chemoresistant lung cancer are of notable clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting assays were performed to analyze the expression levels of phosphatase and tensin homolog (PTEN) and microRNA-4328 (miR-4328), and Cell Counting Kit-8 (CCK-8) and Transwell migration assays were conducted to evaluate the proliferation and migration of A549 cells, respectively. Everolimus was observed to upregulate the expression of PTEN and inhibit the proliferation and migration of A549 cells in a dose-dependent manner.

Involvement of Akt/CREB signaling pathways in the protective effect of EPA against interleukin-1β-induced cytotoxicity and BDNF down-regulation in cultured rat hippocampal neurons.

Background: Our published data have indicated that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating neuronal damage induced by interleukin-1β (IL-1β), and up-regulation of the expression of brain-derived neurotrophic factor (BDNF) represents a crucial part in the neuroprotective effect of EPA. However, the mechanisms of how EPA regulates BDNF expression remains incompletely understood. The present study investigated the role of Akt/CREB signaling in the effect of EPA on BDNF expression and its neuroprotective effect.

MicroRNA-374a Promotes Hepatocellular Carcinoma Cell Proliferation by Targeting Mitogen-Inducible Gene 6 (MIG-6).

Hepatocellular carcinoma (HCC) is a disease with poor prognosis rates and ineffective therapeutic options. Previous studies have reported the involvement of mitogen-inducible gene 6 (MIG-6) as a negative regulator in tumor formation. MicroRNAs (miRNAs) play crucial roles in the development of different types of cancer.

Phytoestrogen α-zearalanol improves memory impairment and hippocampal neurogenesis in ovariectomized mice.

Estrogen is known to provide robust protection of memory in postmenopausal women, but the fact that estrogen may increase the incidence of uterine and breast tumors has undoubtedly limited the clinical use of estrogen. In the present study, the effect of α-zearalanol (α-ZAL), a plant-derived phytoestrogen with low side-effect on uterine and breast, on memory has been evaluated in ovariectomized (OVX) mice when using 17β-estradiol (17β-E2) as an estrogen positive control. Our findings demonstrated that OVX resulted in impaired spatial learning and memory and reduced numbers of newborn neurons in the dentate gyrus of the hippocampus, while 17β-E2 or α-ZAL treatment significantly improved memory performance and restored hippocampal neurogenesis.

The effect of enterovirus 71 immunization on neuropathogenesis and protein expression profiles in the thalamus of infected rhesus neonates.

Enterovirus 71 (EV71) is a major pathogen that causes hand-foot-mouth disease (HFMD). Our previous studies have demonstrated that the complete process of pathogenesis, which may include tissue damage induced by host inflammatory responses and direct tissue damage caused by viral infection, can be observed in the central nervous system (CNS) of animals infected in the laboratory with EV71. Based on these observations, the neuropathogenesis and protein expression profiles in the thalamic tissues of EV71-infected animals were further analyzed in the present study.

Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model.

Purpose: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.

Methods: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling.