Structure-based discovery of pyrazole-benzothiadiazole hybrid as human HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) has attracted increasing attention as a target for treating type I tyrosinemia and other diseases with defects in tyrosine catabolism. Only one commercial drug, 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), clinically treat type I tyrosinemia, but show some severe side effects in clinical application. Here, we determined the structure of human HPPD-NTBC complex, and developed new pyrazole-benzothiadiazole 2,2-dioxide hybrids from the binding of NTBC.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length.

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells.

Leukemia is a fatal hematopoietic disorder with a poor prognosis. Drug resistance is inevitable after the long‑term use of chemotherapeutic agents. Liproxstatin‑1, commonly known as a ferroptosis inhibitor, has never been reported to have anticancer effects.

Amoxicillin-vonoprazan dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

Background And Aim: The efficacy and safety of amoxicillin-vonoprazan (VA) dual therapy remained unclear.

Methods: This systematic review was conducted in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H.

Altered Spontaneous Brain Activity Patterns of Meibomian Gland Dysfunction in Severely Obese Population Measured Using the Fractional Amplitude of Low-Frequency Fluctuations.

Objective: Utilizing the fractional amplitude of low-frequency fluctuations (fALFF) technique, this study sought to correlate spontaneous cerebral abnormalities with the clinical manifestations of meibomian gland dysfunction (MGD) in severely obese (SO) population.

Subjects And Methods: Twelve MGD patients in SO population (PATs) (4 males and 8 females) and twelve healthy controls (HCs) (6 males and 6 females) matched by gender and age were enrolled. Every participant underwent resting-state functional magnetic resonance imaging (rs-MRI) scanning.

Altered White Matter Integrity in Patients with Retinal Vein Occlusion: A Diffusion Tensor Imaging and Tract-Based Spatial Statistics Study.

Background: To investigate microstructural alterations of white matter in retinal vein occlusion (RVO) patients by tract-based spatial statistics (TBSS) and diffusion tensor imaging (DTI). . DTI was performed on 14 RVO patients and 14 normal controls (HCs).

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure.

Folic Acid Inhibited Vasculogenic Mimicry in Esophageal Cancer Cell Line Eca-109, the One Target Was EphA2.

The degree of vasculogenic mimicry(VM) is correlated with the prognosis of esophageal cancer, and folic acid supplementation could decrease esophagus cancer deaths among populations. This study aimed to explore the effect of folic acid on VM formation of esophageal cancer cell, and the target. Human esophageal squamous cancer cell lines(Eca-109) were cultured with different concentrations of folic acid (0,1,10,100,200,400, 600,800 μg/ml).

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy.

Identification and verification of effective components of Huanghuai for dysfunctional uterine bleeding based on network pharmacology and molecular docking.

Objective: The Huanghuai (HH), which is made from the dried roots of (Huangqin in Chinese) and the dried flowers and buds of (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect.

Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.

6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway.

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects.

Guillain-Barré syndrome in a patient with multiple myeloma after bortezomib therapy: A case report.

Background: Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barré syndrome (GBS) is recognized as an immune-mediated PN characterized by the involvement of multiple nerve roots and peripheral nerves and albuminocytologic dissociation in cerebrospinal fluid (CSF) tests.

Cholinesterases and Engineered Mutants for the Detection of Organophosphorus Pesticide Residues.

Nowadays, pesticide residues constitute an increasing public health concern. Cholinesterases, acetylcholinesterase, and butyrylcholinesterase, are reported to be involved in detoxification processes owing to their capability of scavenging organophosphates and carbamates. Thus, these enzymes are targeted for the discovery of sensors aiming at detecting pesticide residues.

Intranasal co-administration of 1,8-cineole with influenza vaccine provide cross-protection against influenza virus infection.

Background: Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection.

[Hand-foot-mouth disease pathogen separation and EV71 VP1 gene analysis in Sanmenxia City, Henan Province, China].

The aim of this study was to understand the enterovirus types and biological features of pediatric cases of HFMD in Sanmenxia City during 2011, and compare the latter to a cohort of healthy children. Stool samples of 55 cases of HFMD and 60 healthy children were collected for the isolation and identification of enteroviruses using RNA extraction and real-time RT-PCR assays. EV71 and CA16 were identified by nucleotide sequencing using virus-specific VP1 primers; for the other enteroviruses, 012/011 and 008/013 primers were used for amplification and sequencing.

Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia. Inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC), has been available for clinical use so far.

Pyrazolone-quinazolone hybrids: a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization.

[The profile of IGF2R gene expression and H3 histone modifications in replicative cell senescence].

Objective: To study the profile of IGF2R expression and histone modifications in replicative cell senescence.

Methods: The changes of biological characteristics of young human pulmonary fibroblast (HPF) cells [at population doubling level (PDL) 23] and aging HPF cells (at PDL50) were observed and real-time quantitative PCR was utilized to investigate human IGF2R gene expressions profile during the process of cellular aging (at different PDL). Then chromatinimmunoprecipitation-real time quantitative PCR (CHIP-QPCR) methods were conducted to analyze histone modifications of the regions around the transcriptional start site of IGF2R (H3-Ac, H3K9-tri-Me, H3K9-Ac and H3K4-tri-Me).

[Comparison of different molecular assays for the rapid detection of enterovirus 71 (EV71)].

Molecular detection of enterovirus (EV)71 RNA based on PCR methods is a quick and sensitive approach. At present, different PCR-based methods for EV71 RNA detection are available, but comparisons of results obtained using different approaches are limited. This study is to compare the analytical sensitivity and specificity of different real-time reverse transcription-polymerase chain reaction (rRT-PCR) and conventional reverse transcription-polymerase chain reaction (cRT-PCR) assays for enterovirus and EV71 detection, Altogether, three rRT-PCR assays and one cRT-PCR assay targeting the 5'UTR gene for universal detection of enterovirus; two rRT-PCR assays andone cRT-PCR assay targeting the VP1 gene for specific detection of EV 71 were examined.

[Etiology surveillance of hand-foot-mouth disease in Henan province between 2008 and 2011].

Objective: To understand etiological types and distribution features of hand-foot-mouth disease (HFMD) in Henan province between 2008 and 2011.

Methods: A total of 30 486 specimens of feces, rectal swabs or throat swabs from HFMD patients were collected by each Municipal CDC in Henan from 2008 to 2011. The enterovirus 71 (EV71), coxsackie virus A16 (CA16) and other enterovirus (EV) were detected by RT-PCR or real time RT-PCR.