Robotic liver resection (RLR) faces challenges in parenchymal dissection due to device limitations, necessitating the development of a safe, efficient, and versatile method for its widespread use. We introduce our six-port RLR approach utilizing the double bipolar clamp-crush method with saline drops to overcome these device limitations. This method, combined with robotic bipolar forceps, maximizes the advantages of RLR by leveraging its multi-joint functionality and facilitates the dissection of strong, fibrotic liver tissue through the use of bipolar energy.
View Article and Find Full Text PDFTwo APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).
View Article and Find Full Text PDFPharmaceuticals (Basel)
August 2024
The damage caused by oxidative and glycative stress to cells accumulates on a daily basis and accelerates aging. Glutathione (GSH), a major antioxidant molecule in living organisms, plays a crucial role in detoxifying the stress-causing substances inherent in cells, such as HO and methylglyoxal (MG), an important intermediate of advanced glycation end-products (AGEs). In this study, we focused on the enhanced antioxidant capacity of the selenium analog of GSH, i.
View Article and Find Full Text PDFBackground: There has been a significant increase in scientific investigations of the hearing-dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use?
Methods: This case-control study performed at two referral centres reported data obtained over a 4.
Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study and expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas is expressed in keratinocytes entering mitosis, we show that expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3).
View Article and Find Full Text PDFSynucleinopathies refer to a group of disorders characterized by SNCA/α-synuclein (α-Syn)-containing cytoplasmic inclusions and neuronal cell loss in the nervous system including the cortex, a common feature being cognitive impairment. Still, the molecular pathogenesis of cognitive decline remains poorly understood, hampering the development of effective treatments. Here, we generated induced pluripotent stem cells (iPSCs) derived from familial Parkinson's disease (PD) patients carrying SNCA A53T mutation, differentiating them into cortical neurons by a direct conversion method.
View Article and Find Full Text PDFHuman papillomaviruses (HPV) cause persistent infections by modulating epithelial homeostasis in cells of the infected basal layer. Using FUCCI and cell-cell competition assays, we have identifed regulatory roles for E6AP and NHERF1, which are the primary HPV11 E6 cellular targets, as well as being targets of the high-risk E6 proteins, in processes governing epithelial homeostasis (i.e.
View Article and Find Full Text PDFHuman papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim > 400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers.
View Article and Find Full Text PDFThe pathophysiology of idiopathic intracranial hypertension (IIH) and idiopathic normal-pressure hydrocephalus (iNPH) differs in terms of cerebrospinal fluid (CSF) pressure and imaging-related characteristics. A 51-year-old man presented with optic nerve papillary edema, visual disturbance, bilateral abducens nerve palsy, and a wide-based gait. Imaging showed characteristic findings of IIH and disproportionately enlarged subarachnoid space hydrocephalus (DESH) - characteristic of iNPH.
View Article and Find Full Text PDFAccumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography.
View Article and Find Full Text PDFBackground/purpose: We evaluated the difficulty score of laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) proposed in the Tokyo guidelines 2018 (TG18) and analyzed the most appropriate scoring method.
Methods: We reviewed 127 patients who underwent LC for AC from January 2018 to March 2022. According to TG18, surgical difficulty was scored for five categories consisting of 25 intraoperative findings.
Mutations within Superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS), accounting for approximately 20% of familial cases. The pathological feature is a loss of motor neurons with enhanced formation of intracellular misfolded SOD1. Homozygous SOD1-D90A in familial ALS has been reported to show slow disease progression.
View Article and Find Full Text PDFBackground: Primary HPV screening, due to its low specificity, requires an additional liquid-based cytology (LBC) triage test. However, even with LBC triage there has been a near doubling in the number of patients referred for colposcopy in recent years, the majority having low-grade disease.
Methods: To counter this, a triage test that generates a spatial map of the cervical surface at a molecular level has been developed which removes the subjectivity associated with LBC by facilitating identification of lesions in their entirety.
Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes.
View Article and Find Full Text PDFBackground: Developing a screening method for mild cognitive impairment in the aging population and intervening early in the progression of dementia based on such a method, remains challenging. Electroencephalography (EEG) is a noninvasive and sensitive tool to assess the functional activity of the brain, and wireless and mobile EEG (wmEEG) could serve as an alternative screening technique that is widely tolerable in patients with dementia from the preclinical to severe stage.
Materials And Methods: Using wmEEG, we recorded bioelectrical activity (BA) from the forehead in 101 individuals with dementia and nondementia controls (NCs) during 4 tasks and investigated which task could differentiate dementia from NC.
Human Papillomaviruses have co-evolved with their human host, with each of the over 200 known HPV types infecting distinct epithelial niches to cause diverse disease pathologies. Despite the success of prophylactic vaccines in preventing high-risk HPV infection, the development of HPV anti-viral therapies has been hampered by the lack of enzymatic viral functions, and by difficulties in translating the results of in vitro experiments into clinically useful treatment regimes. In this review, we discuss recent advances in anti-HPV drug development, and highlight the importance of understanding persistent HPV infections for future anti-viral design.
View Article and Find Full Text PDFPapillomaviruses exclusively infect stratified epithelial tissues and cause chronic infections. To achieve this, infected cells must remain in the epithelial basal layer alongside their uninfected neighbors for years or even decades. To examine how papillomaviruses achieve this, we used the MmuPV1 (Mus musculus papillomavirus 1) model of lesion formation and persistence.
View Article and Find Full Text PDFBackground: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear.
Materials And Methods: We estimated the prevalence of two enterohepatic non-H.