Antisense oligonucleotide therapeutic approach for Timothy syndrome.

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A.

Erratum: [Corrigendum] Cross regulation of signaling pathways in gastrointestinal stromal tumor.

[This corrects the article DOI: 10.3892/ol.2018.

A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels.

Loss-of-function mutations in cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.

Assembloid CRISPR screens reveal impact of disease genes in human neurodevelopment.

The assembly of cortical circuits involves the generation and migration of interneurons from the ventral to the dorsal forebrain, which has been challenging to study at inaccessible stages of late gestation and early postnatal human development. Autism spectrum disorder and other neurodevelopmental disorders (NDDs) have been associated with abnormal cortical interneuron development, but which of these NDD genes affect interneuron generation and migration, and how they mediate these effects remains unknown. We previously developed a platform to study interneuron development and migration in subpallial organoids and forebrain assembloids.

Application and curative effect of laparoscopic purse-string sutures in the treatment of adult acute complicated appendicitis.

Objective: To investigate the effect of laparoscopic purse-string sutures in adult complicated appendicitis treatment.

Methods: The data of 568 adult cases of complicated appendicitis treated by laparoscopic appendectomy at the Hefei Second People's Hospital, Anhui Province, China, from September 2018 to September 2021 were analysed retrospectively. The patients were divided into two groups: 295 cases in the laparoscopic purse-string suture treatment group (observation group) and 273 cases in the simple Hem-o-lok clamp treatment group (control group).

Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication.

Numerous viruses manipulate host factors for viral production. We demonstrated that human enterovirus A71 (EVA71), a primary causative agent for hand, foot, and mouth disease (HFMD), increased the level of the DNA damage response (DDR) marker γ-H2AX. DDR is primarily mediated by the ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), or DNA-dependent protein kinase (DNA-PK) pathways.

The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C.

Lysosome dysfunction is a shared feature of rare lysosomal storage diseases and common age-related neurodegenerative diseases. Microglia, the brain-resident macrophages, are particularly vulnerable to lysosome dysfunction because of the phagocytic stress of clearing dying neurons, myelin, and debris. CD22 is a negative regulator of microglial homeostasis in the aging mouse brain, and soluble CD22 (sCD22) is increased in the cerebrospinal fluid of patients with Niemann-Pick type C disease (NPC).

Efficacy and safety of mesenchymal stem cell in Chinese patients with chronic renal failure: A pilot study in Shandong province, China.

This study designed to evaluate efficacy and safety profile of Mesenchymal stem cells (MSCs) versus Acetyl cysteine (NACys) in the Chinese patients with Chronic renal failure (CRF). The CRF patients having eGFR less than 60ml per minute per 1.73m2 randomly assigned to MSCs (N=100) or NACys (N=100) (1:1) for 8 weeks.

Circ_002059 suppresses cell proliferation and migration of gastric cancer via miR-182/MTSS1 axis.

Circular RNAs (circRNAs) play either oncogenic or tumor suppressive roles in gastric cancer (GC). A previous study demonstrated that circ_002059, a typical circRNA, was downregulated in GC tissues. However, the role and mechanism of circ_002059 in GC development are still unknown.

Loss of MeCP2 Function Across Several Neuronal Populations Impairs Breathing Response to Acute Hypoxia.

Rett Syndrome (RTT) is a neurodevelopmental disorder caused by loss of function of the transcriptional regulator Methyl-CpG-Binding Protein 2 (MeCP2). In addition to the characteristic loss of hand function and spoken language after the first year of life, people with RTT also have a variety of physiological and autonomic abnormalities including disrupted breathing rhythms characterized by bouts of hyperventilation and an increased frequency of apnea. These breathing abnormalities, that likely involve alterations in both the circuitry underlying respiratory pace making and those underlying breathing response to environmental stimuli, may underlie the sudden unexpected death seen in a significant fraction of people with RTT.

Downregulating circRNA_0044516 Inhibits Cell Proliferation in Gastric Cancer Through miR-149/Wnt1/β-catenin Pathway.

Background: Circular RNAs (circRNAs) play important roles in the progression of gastric cancer (GC). The Wnt1/β-catenin pathway can promote the proliferation of GC cells. This study aimed to explore whether circRNA_0044516 can regulate the proliferation of GC cells by modulating the Wnt1/β-catenin pathway.

Caspase-3 inhibitor inhibits enterovirus D68 production.

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production.

CircRNA-PTN Sponges miR-326 to Promote Proliferation in Hepatocellular Carcinoma.

Background: Mounting evidences reveal that circular RNAs (circRNAs) are critical to regulate biological behavior and process of tumor. Our objective is to explore the role of circRNA-PTN (circPTN) and explain the exact mechanism in hepatocellular carcinoma (HCC).

Methods: Real-time polymerase chain reaction assay was used to detect the level of circPTN and miR-326.

Impact of Nutritional Indices on the Survival Outcomes of Patients with Colorectal Cancer.

Background: The effect of preoperative nutritional status on the survival of patients with colorectal cancer is still unknown. The purpose of our study was to examine the impact of the prognostic nutritional index (PNI), prealbumin (PAB) and the albumin to globulin ratio (AGR) on survival outcomes in patients with colon and rectal cancer.

Methods: Between January 2012 and December 2013, 361 patients with colorectal cancer who underwent curative surgery in the survey and various clinical and haematological parameters were recorded.

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.

Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens.

Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis.

Coxsackievirus A6 Induces Necroptosis for Viral Production.

Hand, foot, and mouth disease (HFMD) is a febrile exanthematous disease with typical or atypical symptoms. Typical HFMD is usually caused by enterovirus 71 (EV71) or coxsackievirus A16, while atypical HFMD is usually caused by coxsackievirus A6 (CA6). In recent years, worldwide outbreaks of CA6-associated HFMD have dramatically increased, although the pathogenic mechanism of CA6 is still unclear.

Bursectomy Versus Nonbursectomy for Gastric Adenocarcinoma: A Single-Center, Propensity-Score Matched Cohort Study in China.

The therapeutic value of bursectomy remains controversial for patients with gastric cancer. Therefore, the purpose of our study was to explore the safety and survival benefits of bursectomy. A total of 943 patients with gastric adenocarcinoma were included in our study, and all patients were operated on by high-quality gastrointestinal surgeons.

The combined effect of oleonuezhenide and wedelolactone on proliferation and osteoblastogenesis of bone marrow mesenchymal stem cells.

Background: Regulation of the survival and differentiation of bone marrow mesenchymal stem cells is an essential consideration in the development of targeted drugs for treatment of osteoporosis.

Purpose: The present study aimed to evaluate the combined effect of wedelolactone and oleonuezhenide, two compounds from Chinese formula Er-Zhi-Wan, on osteoblastogenesis and the underlying molecular mechanisms.

Methods: MTT assay was taken to evaluate cell proliferation.

LncRNA CASC9 Suppressed the Apoptosis of Gastric Cancer Cells through Regulating BMI1.

Long noncoding RNAs (lncRNAs) play important roles in regulating the apoptosis of gastric cancer (GC) cells. This study aims to investigate the underlying mechanism of lncRNA CASC9 in regulating the apoptosis of GC cells. The expressions of lncRNA and protein in GC tissues and cell lines were detected by qRT-PCR and western blot.

Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions.

Neurexophilins are secreted neuropeptide-like glycoproteins, and neurexophilin1 and neurexophilin3 are ligands for the presynaptic cell adhesion molecule α-neurexin. Neurexophilins are more selectively expressed in the brain than α-neurexins, however, which led us to ask whether neurexophilins modulate the function of α-neurexin in a context-specific manner. We characterized the expression and function of neurexophilin4 in mice and found it to be expressed in subsets of neurons responsible for feeding, emotion, balance, and movement.

Differential expression profile analysis of cisplatin‑regulated miRNAs in a human gastric cancer cell line.

Cisplatin, one of the most commonly used drugs in combination chemotherapy, is an effective anti‑tumor agent widely used for diverse tumor types. MicroRNAs (miRNAs/miRs) are involved in the occurrence, development, diagnosis and treatment of cancer. Therefore, the aim of the current study was to explore whether cisplatin exerts anticancer effects by causing differential expression of miRNAs in human gastric cancer cells.

Naringenin ameliorates insulin resistance by modulating endoplasmic reticulum stress in hepatitis C virus-infected liver.

Hepatitis C virus (HCV) infection may lead to hepatic insulin resistance (IR), and endoplasmic reticulum (ER) stress has been found to induce IR. In our previous study, naringenin (NGEN) had an insulin sensitization effect on the HCV core protein (HCVCP) infected mouse livers. In the present study, we examined the effects of NGEN on HCVCP infection-induced ER stress and investigated the insulin sensitization mechanism involved.

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway.

BACKGROUND Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved.