Preferential Cochleotoxicity involving Cisplatin

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. CircZKSCAN1 (hsa_circ_0001727) was reported to be related to HCC development. The present study aims to elucidate the potential role and molecular mechanism of circZKSCAN1 in the regulation of HCC progression.
CircZKSCAN1, miR-873-5p, and downregulation of deleted in liver cancer 1 (DLC1) in HCC tissues and cells were detected by RT-qPCR. Correlation between circZKSCAN1 expression and overall survival rate was measured by Kaplan-Meier survival analysis. The effects of circZKSCAN1, miR-873-5p, and DLC1 on proliferation, migration, and invasion were analyzed by CCK-8 and transwell assays, respectively. CyclinD1, Matrix metalloproteinase (MMP)-9, MMP-2, and DLC1 in HCC cells were detected by Western blot assay. The binding relationship between miR-873-5p and circZKSCAN1 or DLC1 was predicted by the Circinteractome or Starbase, and then confirmed by dual-luciferase reporter assays, respectively. Tumor volume and tumor weight were measured in vivo.
CircZKSCAN1 was downregulated in HCC tissues and cells. Kaplan-Meier survival analysis suggested that there was a positive correlation between circZKSCAN1 expression and overall survival rate. Functionally, circZKSCAN1 blocked proliferation, migration, and invasion of HCC cells. MiR-873-5p was a target miRNA of circZKSCAN1, and miR-873-5p directly bound with DLC1. Rescue experiments confirmed that miR-873-5p overexpression or DLC1 knockdown attenuated the suppressive effects of circZKSCAN1 on HCC tumor growth in vitro. Besides, circZKSCAN1 inhibited HCC cell growth in vivo.
This study firstly revealed that circZKSCAN1 curbed HCC progression via modulating miR-873-5p/DLC1 axis, providing a potential therapeutic target for HCC treatment.
This study firstly revealed that circZKSCAN1 curbed HCC progression via modulating miR-873-5p/DLC1 axis, providing a potential therapeutic target for HCC treatment.
Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity.
The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia.
The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013-February 2016 were prospectively evaluated.
The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m
. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy.
The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.
The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders which involve the corticospinal tracts and present with distinct spasticity and weakness of the lower extremities. The estimated prevalence of HSP is around 1.8/100,000 cases for both autosomal dominant and autosomal recessive types. Classification of HSP is based on inheritance pattern, clinical phenotype, and molecular pathophysiological mechanisms. PF-07321332 The most common neuropathological sign is the axonal degeneration involving the lateral corticospinal tracts in both the cervical and thoracic spinal cord. The target of this review article is to provide a comprehensive overview of the HSP classification, neuropathology, and differential diagnosis.
Recessive mutations in the SLC4A4 gene cause a syndrome characterised by proximal renal tubular acidosis (pRTA), mental retardation, dental and ocular abnormalities, and hemiplegic migraine. Rare cases involving the development of epilepsy or its severe complication-status epilepticus-have been described.
The clinical and genetic status of four affected members in a Spanish family was studied. The SLC4A4 gene mutation was detected with a next-generation sequencing (NGS) panel in the proband, and Sanger confirmed the putative mutations in affected relatives. In silico analysis was performed to elucidate the putative effect of mutation on the splicing process.
A novel mutation, c.2562+2T>G, was identified in the homozygous state in all diseased members of the family. This mutation affected a canonical splice site and is predicted to abolish the wild-type donor site, which predicts a premature truncated NBCe1 protein with cotransport activity. The resulting protein lacks the 190 amino acids of the carboxyl-terminus, and the effect is likely to be a loss of function. All patients suffered from severe pRTA and ocular abnormalities, and the adults also suffered from neurological complications, such as hemiplegic migraine and/or epilepsy. Two developed life-threatening status epilepticus, although they fully recovered and remained free of seizures with valproate.
These results expand the clinical and mutational spectra of SLC4A4-related disease and have implications for understanding the potential role of NBCe1 in the pathophysiologic processes of hemiplegic migraine and epilepsy/status epilepticus associated with the mutation.
These results expand the clinical and mutational spectra of SLC4A4-related disease and have implications for understanding the potential role of NBCe1 in the pathophysiologic processes of hemiplegic migraine and epilepsy/status epilepticus associated with the mutation.