bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of six hub genes and two key pathways in two rat renal fibrosis models based on bioinformatics and RNA-seq transcriptome analyses
Authors: Cai Yueqin , Chen Jingan , Liu Jingyan , Zhu Keyan , Xu Zhixing , Shen Jianan , Wang Dejun , Chu Lisheng
Published: November 2022

Renal fibrosis (RF) is the common pathological manifestation and central treatment target of multiple chronic kidney diseases with high morbidity and mortality. Currently, the molecular mechanisms underlying RF remain poorly understood, and exploration of RF-related hub targets and pathways is urgently needed. In this study, two classical RF rat models (adenine and UUO) were established and evaluated by HE, Masson and immunohistochemical staining. To clear molecular mechanisms of RF, differentially expressed genes (DEGs) were identified using RNA-Seq analysis, hub targets and pathways were screened by bioinformatics (functional enrichment analyses, PPI network, and co-expression analysis), the screening results were verified by qRT-PCR, and potential drugs of RF were predicted by network pharmacology and molecular docking. The results illustrated that renal structures were severely damaged and fibrotic in adenine- and UUO-induced models, as evidenced by collagen deposition, enhanced expressions of biomarkers (TGF-β1 and α-SMA), reduction of E-cadherin biomarker, and severe renal function changes (significantly decreased UTP, CREA, Ccr, and ALB levels and increased UUN and BUN levels), etc. 1189 and 1253 RF-related DEGs were screened in the adenine and UUO models, respectively. Two key pathways (AGE-RAGE and NOD-like receptor) and their hub targets (Tgfb1, Col1a1, Nlrc4, Casp4, Trpm2, and Il18) were identified by PPI networks, co-expressed relationships, and qRT-PCR verification. Furthermore, various reported herbal ingredients (curcumin, resveratrol, honokiol, etc.) were considered as important drug candidates due to the strong binding affinity with these hub targets. Overall, this study mainly identified two key RF-related pathways (AGE-RAGE and NOD-like receptor), screened hub targets (Tgfb1, Col1a1, Nlrc4, Casp4, Trpm2, and Il18) that involved inflammation, ECM formation, myofibroblasts generation, and pyroptosis, etc., and provided referable drug candidates (curcumin, resveratrol, honokiol, etc.) in basic research and clinical treatment of RF.
The Effect of Aging on Retinal Function and Retinal Ganglion Cell Morphology Following Intraocular Pressure Elevation
Authors: Lee Pei Ying , Zhao Da , Wong Vickie H. Y. , Chrysostomou Vicki , Crowston Jonathan G. , Bui Bang V.
Published: November 2022

Aging and elevated intraocular pressure (IOP) are two major risk factors for glaucomatous optic neuropathy; a condition characterized by the selective, progressive injury, and subsequent loss of retinal ganglion cells (RGCs). We examined how age modified the capacity for RGCs to functionally recover following a reproducible IOP elevation (50 mmHg for 30 min). We found that RGC functional recovery (measured using electroretinography) was complete by 7 days in 3-month-old mice but was delayed in 12-month-old mice until 14 days. At the 7-day recovery endpoint when RGC function had recovered in young but not older eyes, we examined RGC structural responses to IOP-related stress by analyzing RGC dendritic morphology. ON-RGC cell volume was attenuated following IOP elevation in both young and older mice. We also found that following IOP elevation OFF-RGC dendritic morphology became less complex per cell volume in young mice, an effect that was not observed in older eyes. Our data suggest that adaptations in OFF-RGCs in young eyes were associated with better functional recovery 7 days after IOP elevation. Loss of RGC cellular adaptations may account for delayed functional recovery in older eyes.
The relationship between Alzheimer’s disease and intestinal microflora structure and inflammatory factors
Authors: Wang Su-shan , Li Xiao-hui , Liu Ping , Li Jing , Liu Li
Published: November 2022

To analyze the structural characteristics of intestinal microflora and changes of serum inflammatory factors of the Alzheimer’s disease, and to explore the relationship between them and dementia, we selected 30 patients in the AD group and 30 patients in the normal group, and collected stool samples to analyze the intestinal flora structure characteristics of the two groups of patients, and statistically analyzed the inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8 by ELISA from the venous blood of the two groups. The results show that the dominant Bacteroides in the two groups are Bacteroides, Firmicutes, Proteobacteria, and Actinobacteria. The abundance of Bacteroides, Firmicutes, and Proteobacteria in the AD group shows a statistical difference. At the genus level, the abundance of anti-inflammatory bacteria such as Lactobacillus, Bifidobacterium, and Ruminococcus drops in AD group, while the abundance of pro-inflammatory bacteria such as Escherichia and Enterococcus raises. Statistical analysis of inflammatory cytokines in the two groups suggests that TNF-α and IL-6 levels significantly increase in the AD group, with statistical differences. Therefore, it is speculated that the increased abundance of pro-inflammatory bacteria in intestinal flora may lead to or aggravate neuroinflammation through the release of inflammatory factors, thus further leading to the occurrence and development of AD.
The effects of bilateral prostriata lesions on spatial learning and memory in the rat
Authors: Zhang Shun-Yu , Chen Sheng-Qiang , Zhang Jin-Yuan , Chen Chang-Hui , Xiang Xiao-Jun , Cai Hui-Ru , Ding Song-Lin
Published: November 2022

Area prostriata is the primary limbic structure for rapid response to the visual stimuli in the far peripheral visual field. Recent studies have revealed that the prostriata receives inputs not only from the visual and auditory cortices but also from many structures critical for spatial processing and navigation. To gain insight into the functions of the prostriata in spatial learning and memory the present study examines the effects of bilateral lesions of the prostriata on motor ability, exploratory interest and spatial learning and memory using the open field, elevated plus-maze and Morris water maze tests. Our results show that the spatial learning and memory abilities of the rats with bilateral prostriata lesions are significantly reduced compared to the control and sham groups. In addition, the lesion rats are found to be less interested in space exploration and more anxious while the exercise capacity of the rats is not affected based on the first two behavioral tests. These findings suggest that the prostriata plays important roles in spatial learning and memory and may be involved in anxiety as well.
Outcome devaluation by specific satiety disrupts sensory-specific Pavlovian-to-instrumental transfer
Authors: Panayi Marios C. , Killcross Simon
Published: November 2022

Reward predictive cues can selectively motivate instrumental behaviors that predict the same rewarding outcomes, an effect known as specific Pavlovian-to-instrumental transfer (PIT). This selective effect is thought to be mediated by a representation of the sensory specific properties of an outcome, that has become associated with both the Pavlovian cue and the instrumental response during initial learning. Specific satiety is a common method of outcome devaluation that reduces an outcome's value but might also lead to the habituation of the outcome's sensory properties. Previous research has demonstrated that specific PIT is insensitive to changes in specific outcome value following taste aversion devaluation, as well as general satiety manipulations, and therefore specific satiety should not disrupt specific PIT by reducing outcome value. The present rodent experiments used a specific satiety devaluation procedure immediately prior to a specific PIT test to show that habituation of these outcome specific sensory representations can disrupt its efficacy as a stimulus and abolish the specific PIT effect. Experiment 1 employed a two-lever choice test to show that a non-devalued stimulus supports specific PIT, whereas a devalued stimulus abolished the specific PIT effect. Experiment 2 replicated this procedure while controlling for response competition by using a single-lever test to confirm that a devalued stimulus abolishes the specific PIT effect. These findings demonstrate that specific satiety can disrupt the ability of an outcome specific representation to support specific PIT. Given previous findings that specific PIT is insensitive to changes in outcome value by general satiety and taste aversion devaluation, this suggests that specific satiety devaluation might disrupt the use of sensory specific outcome representations to guide behavior via a mechanism that is independent of the outcome's current value.
Ischemic stroke: From pathological mechanisms to neuroprotective strategies
Authors: Jiang Yang , Liu Zhenquan , Liao Yan , Sun Shuyong , Dai Yajie , Tang Yibo
Published: November 2022

Ischemic stroke (IS) has complex pathological mechanisms, and is extremely difficult to treat. At present, the treatment of IS is mainly based on intravenous thrombolysis and mechanical thrombectomy, but they are limited by a strict time window. In addition, after intravenous thrombolysis or mechanical thrombectomy, damaged neurons often fail to make ideal improvements due to microcirculation disorders. Therefore, finding suitable pathways and targets from the pathological mechanism is crucial for the development of neuroprotective agents against IS. With the hope of making contributions to the development of IS treatments, this review will introduce (1) how related targets are found in pathological mechanisms such as inflammation, excitotoxicity, oxidative stress, and complement system activation; and (2) the current status and challenges in drug development.
Pathogenesis, diagnosis and therapy of facial synkinesis: A systematic review and clinical practice recommendations by the international head and neck scientific group
Authors: Guntinas-Lichius Orlando , Prengel Jonas , Cohen Oded , Mäkitie Antti A. , Vander Poorten Vincent , Ronen Ohad , Shaha Ashok , Ferlito Alfio
Published: November 2022

Introduction

Post-paralytic facial synkinesis after facial nerve injury produces functional disabilities and mimetic deficits, but also cosmetic and non-motor psychosocial impairments for the patients. These patients typically have a high and continuous high motivation for rehabilitation. The aim is to inform the affected patients and their therapeutic professionals (otorhinolaryngologist - head and neck surgeons; oral-maxillofacial surgeons, plastic and reconstructive surgeons, neurosurgeons, neurologists, and mime therapists be it speech and language therapy- or physiotherapy-based) and to provide practical recommendations for diagnostics and a stepwise systematic treatment approach of facial synkinesis.

Methods

In the first phase, a systematic literature search on the topic in PubMed and ScienceDirect starting in 2008 resulted in 132 articles. These were the basis for the review and a comprehensive series of consensus statements on the most important diagnostic tests and treatment options. In the second phase, one consensus article circulated among the membership of the International Head and Neck Scientific Group until a final agreement was reached for all recommendations.

Results

Diagnostics should include a standardized assessment of the degree of synkinesis using validated clinician-graded instruments and synkinesis-specific patient-reported outcome measures. Treatments for facial synkinesis include facial training mainly based on facial biofeedback retraining, chemodenervation with botulinum toxin, selective neurectomy, myectomy, and any combination treatment of these options.

Conclusion

A basic understanding of the pathomechanisms of synkinesis is essential to understand the treatment strategies. A standardized assessment of the synkinetic symptoms and the individual synkinesis pattern is needed. The first-line treatment is facial training, followed by botulinum toxin. Surgery is reserved for individual cases with unsatisfactory first-line treatment.
Endovascular treatment of an aneurysm associated with fenestration of the supraclinoid internal carotid artery: Case report and review of the literature
Authors: Filep Rareṣ Cristian , Constantin Cristian , Arbǎnaṣi Emil Marian , Mureṣan Adrian Vasile , Russu Eliza , Mǎrginean Lucian
Published: November 2022

Background

Fenestrations or divisions of the vascular lumen into separate channels appear to be common anatomical variations in patients with intracranial aneurysms. The most frequent sites of occurrence are the anterior communicating artery (ACom), followed by vertebrobasilar and middle cerebral artery (MCA) locations.

Case presentation

A 61-year-old female was brought to the emergency department after experiencing severe headache with abrupt onset, nausea, and vomiting. Clinical examination on arrival showed a drowsy patient (GCS 14), with neck stiffness, but no cranial nerve palsies or other neurological deficits (Hunt-Hess 2). Non-contrast head CT and CT angiography revealed subarachnoid and intraventricular hemorrhage (modified Fisher 4) and two saccular aneurysms, one located on the right supraclinoid ICA with peripheral calcifications, measuring 20 × 12 mm, the second on the left MCA bifurcation, 6 × 4 mm. 3D rotational angiography revealed a right ICA fenestration located between the ophthalmic (OA) and posterior communicating artery (PCom). The proximal part of the fenestration harbored a large saccular aneurysm projecting superiorly with the neck engulfing the origin of the fenestration; due to the favorable neck and geometry of the aneurysm, endovascular coil occlusion was chosen as a treatment option without balloon or stent assistance. The decision was taken to clip the MCA aneurysm.

Conclusion

Supraclinoid ICA fenestrations are rare anatomical variations. Endovascular treatment of supraclinoid ICA fenestration-related aneurysms is feasible and safe, with the notable concern of perforators originating from the limbs.
Bridging the gap of axonal regeneration in the central nervous system: A state of the art review on central axonal regeneration
Authors: Costa Gonçalo , Ribeiro Filipa F. , Sebastião Ana M. , Muir Elizabeth M. , Vaz Sandra H.
Published: November 2022

Neuronal regeneration in the central nervous system (CNS) is an important field of research with relevance to all types of neuronal injuries, including neurodegenerative diseases. The glial scar is a result of the astrocyte response to CNS injury. It is made up of many components creating a complex environment in which astrocytes play various key roles. The glial scar is heterogeneous, diverse and its composition depends upon the injury type and location. The heterogeneity of the glial scar observed in different situations of CNS damage and the consequent implications for axon regeneration have not been reviewed in depth. The gap in this knowledge will be addressed in this review which will also focus on our current understanding of central axonal regeneration and the molecular mechanisms involved. The multifactorial context of CNS regeneration is discussed, and we review newly identified roles for components previously thought to solely play an inhibitory role in central regeneration: astrocytes and p75NTR and discuss their potential and relevance for deciding therapeutic interventions. The article ends with a comprehensive review of promising new therapeutic targets identified for axonal regeneration in CNS and a discussion of novel ways of looking at therapeutic interventions for several brain diseases and injuries.
Increased resting-state alpha coherence and impaired inhibition control in young smokers
Authors: Wang Zhengxi , Dong Fang , Sun Yaning , Wang Juan , Zhang Ming , Xue Ting , Ren Yan , Lv Xiaoqi , Yuan Kai , Yu Dahua
Published: November 2022

Exposure to nicotine is the first cause of entirely preventable death killing, which is commonly initiated in adolescence. Previous studies revealed the changes of electroencephalography (EEG) and inhibition control in smokers. However, little is known about the specific link between alpha coherence during the resting state and inhibition control ability in young smokers. The present study aimed to investigate inter-hemispherical and frontal-parietal alpha coherence changes and assessed the relationships between alpha coherence and inhibition control in young smokers. We collected resting-state EEG data from 23 young smokers and 24 healthy controls. Inhibition control ability was assessed by a Go/NoGo task. Compared to healthy controls, young smokers exhibited increased inter-hemispherical and frontal-parietal alpha coherence. Furthermore, young smokers committed more NoGo errors in the Go/NogGo task. It is noteworthy that alpha coherence at the frontal electrode sites was positively correlated with NoGo errors in healthy controls, whereas inverse correlations were observed in young smokers. Our findings suggested that alterations of alpha coherence may provide support to the earlier nicotine-dependence-related research findings, which may help us to understand the neuropathology of inhibitory control in young smokers.
Alteration of muscle activity during voluntary rehabilitation training with single-joint Hybrid Assistive Limb (HAL) in patients with shoulder elevation dysfunction from cervical origin
Authors: Lafitte Margaux Noémie , Kadone Hideki , Kubota Shigeki , Shimizu Yukiyo , Tan Chun Kwang , Koda Masao , Hada Yasushi , Sankai Yoshiyuki , Suzuki Kenji , Yamazaki Masashi
Published: November 2022

Shoulder elevation, defined here as arm raising, being essential for activities of daily living, dysfunctions represent a substantial burden in patients’ lives. Owing to the complexity of the shoulder joint, the tightly coordinated muscular activity is a fundamental component, and neuromuscular impairments have devastating effects. A single-joint shoulder type version of the Hybrid Assistive Limb (HAL) allowing motion assistance based on the intention of the user via myoelectric activation has recently been developed, and its safety was demonstrated for shoulder rehabilitation. Yet, little is known about the physiological effects of the device. This study aims to monitor the changes in muscle activity and motion during shoulder HAL rehabilitation in several patients suffering from shoulder elevation dysfunction from cervical radicular origin. 8 patients (6 males, 2 females, mean age 62.4 ± 9.3 years old) with weakness of the deltoid muscle resulting from a damage to the C5 nerve root underwent HAL-assisted rehabilitation. We combined surface electromyography and three-dimensional motion capture to record muscular activity and kinematics. All participants showed functional recovery, with improvements in their Manual Muscle Testing (MMT) scores and range of motion (ROM). During training, HAL decreased the activity of deltoid and trapezius, significantly more for the latter, as well as the coactivation of both muscles. We also report a reduction of the characteristic shrugging compensatory motion which is an obstacle to functional recovery. This reduction was notably demonstrated by a stronger reliance on the deltoid rather than the trapezius, indicating a muscle coordination tending toward a pattern similar to healthy individuals. Altogether, the results of the evaluation of motion and muscular changes hint toward a functional recovery in acute, and chronic shoulder impairments from cervical radicular origin following shoulder HAL rehabilitation training and provide information on the physiological effect of the device.
Peripheral role of glutamate in orofacial pain
Authors: Liu Jinyue , Jia Shilin , Huang Fang , He Hongwen , Fan Wenguo
Published: November 2022

Glutamate is the principal excitatory neurotransmitter in the central nervous system. In the periphery, glutamate acts as a transmitter and involves in the signaling and processing of sensory input. Glutamate acts at several types of receptors and also interacts with other transmitters/mediators under various physiological and pathophysiological conditions including chronic pain. The increasing amount of evidence suggests that glutamate may play a role through multiple mechanisms in orofacial pain processing. In this study, we reviewed the current understanding of how peripheral glutamate mediates orofacial pain, how glutamate is regulated in the periphery, and how these findings are translated into therapies for pain conditions.
Intestinal microbiota and melatonin in the treatment of secondary injury and complications after spinal cord injury
Authors: Zhang Yiwen , Lang Rui , Guo Shunyu , Luo Xiaoqin , Li Huiting , Liu Cencen , Dong Wei , Bao Changshun , Yu Yang
Published: November 2022

Spinal cord injury (SCI) is a central nervous system (CNS) disease that can cause sensory and motor impairment below the level of injury. Currently, the treatment scheme for SCI mainly focuses on secondary injury and complications. Recent studies have shown that SCI leads to an imbalance of intestinal microbiota and the imbalance is also associated with complications after SCI, possibly through the microbial-brain-gut axis. Melatonin is secreted in many parts of the body including pineal gland and gut, effectively protecting the spinal cord from secondary damage. The secretion of melatonin is affected by circadian rhythms, known as the dark light cycle, and SCI would also cause dysregulation of melatonin secretion. In addition, melatonin is closely related to the intestinal microbiota, which protects the barrier function of the gut through its antioxidant and anti-inflammatory effects, and increases the abundance of intestinal microbiota by influencing the metabolism of the intestinal microbiota. Furthermore, the intestinal microbiota can influence melatonin formation by regulating tryptophan and serotonin metabolism. This paper summarizes and reviews the knowledge on the relationship among intestinal microbiota, melatonin, and SCI in recent years, to provide new theories and ideas for clinical research related to SCI treatment.
Structural changes and molecular mechanism study on the inhibitory activity of epigallocatechin against α-glucosidase and α-amylase
Authors: Man Ziyi , Feng Yi , Xiao Jibo , Yang Hailong , Wu Xiangting
Published: November 2022

In this study, the inhibition and mechanism of epigallocatechin (EGC) on two key glycoside hydrolases (α-glucosidase, α-amylase) were explored from the molecular structure level. The chemical structure of EGC was characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and proton nuclear magnetic resonance spectroscopy. EGC’s inhibition on these enzymes was colorimetrically determined. The effects of EGC on the chemical structure and spatial configuration of the enzymes were explored via FTIR spectroscopy, fluorescence spectroscopy, and molecular docking techniques. The results showed that EGC exhibited the inhibition of α-glucosidase and α-amylase in a non-competitive manner, showing a continuous upward trend as EGC’s concentration increased. There was a fluorescence quenching effect of EGC on α-glucosidase and α-amylase. Molecular docking confirmed that EGC can bind to amino acid residues in the enzyme through intermolecular hydrogen bonds and hydrophobic interactions, resulting in the changed chemical structure and spatial conformation of the enzymes. This decreased enzyme activity. This result suggested that EGC has the potential to inhibit two key glycoside hydrolases, and it would be beneficial to incorporate EGC into functional foods for diabetics.
Assessing causal relationships between sarcopenia and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study
Authors: Zhao Ze-Hua , Zou Juanjuan , Huang Xin , Fan Yu-Chen , Wang Kai
Published: November 2022

Background and aims

Sarcopenia has been demonstrated to be closely associated with nonalcoholic fatty liver disease (NAFLD). However, whether there are causal relationships between sarcopenia and NAFLD remains undetermined. Here, we aim to address the question using a two-sample bidirectional Mendelian randomization (MR) analysis approach.

Methods

We performed a two-sample bidirectional MR study using summary-level data from genome-wide association studies (GWAS) of the whole body lean mass (n = 38,292), appendicular (arms and legs) lean mass (n = 28,330), and NAFLD (1,483 biopsy-proven NAFLD cases and 17,781 controls). We first conducted MR analysis with five single nucleotide polymorphisms (SNPs) as genetic instruments for whole body lean mass and three SNPs as instruments for appendicular lean mass to estimate the causal effect of genetically predicted sarcopenia on the risk of NAFLD using the inverse-variance weighted (IVW) method. Then we performed reverse MR analysis with four SNPs as instruments to examine the causality of genetically predicted NAFLD with whole body lean mass and appendicular lean mass. Further sensitivity analysis was conducted to testify the reliability of the MR results.

Results

Genetic predisposition to decreased whole body lean mass was not associated with NAFLD [IVW-random effects, odds ratio (OR) = 1.054, 95%CI: 0.750–1.482, P = 0.761]. Similar results were observed using genetic instruments of appendicular lean mass (IVW-random effects, OR = 0.888, 95%CI: 0.386–2.042, P = 0.780). Reverse MR analysis revealed that genetically predicted NAFLD using four genetic instruments was not associated with whole body lean mass (IVW, β = −0.068, 95%CI: −0.179 to 0.043, P = 0.229) and appendicular lean mass (IVW, β = −0.020, 95%CI: −0.092 to 0.051, P = 0.574). MR analyses using other methods and sensitivity analysis showed consistent results.

Conclusion

These results suggested no causal relationships between sarcopenia and NAFLD, indicating that sarcopenia may not be directly involved in the pathogenesis of NAFLD and vice versa.
Overview on population screening for carriers with germline BRCA mutation in China
Authors: Lei Huijun , Zhang Min , Zhang Luyao , Hemminki Kari , Wang Xiao-jia , Chen Tianhui
Published: November 2022

Carriers with BRCA1/2 germline pathogenic variants are associated with a high risk of breast and ovarian cancers (also pancreatic and prostate cancers). While the spectrum on germline BRCA mutations among the Chinese population shows ethnic specificity, the identification of carriers with germline BRCA mutation before cancer onset is the most effective approach to protect them. This review focused on the current status of BRCA1/2 screening, the surveillance and prevention measures, and discussed the issues and potential impact of BRCA1/2 population screening in China. We conducted literature research on databases PubMed and Google Scholar, as well as Chinese databases CNKI and Wangfang Med Online database (up to 31 March 2022). Latest publications on germline BRCA1/2 prevalence, spectrum, genetic screening as well as carrier counseling, surveillance and prevention were captured where available. While overall 15,256 records were retrieved, 72 publications using germline BRCA1/2 testing were finally retained for further analyses. Germline BRCA1/2 mutations are common in Chinese patients with hereditary breast, ovarian, prostate and pancreatic cancers. Within previous studies, a unique BRCA mutation spectrum in China was revealed. Next-generation sequencing panel was considered as the most common method for BRCA1/2 screening. Regular surveillance and preventive surgeries were tailored to carriers with mutated-BRCA1/2. We recommend that all Chinese diagnosed with breast, ovarian, pancreatic or prostate cancers and also healthy family members, shall undergo BRCA1/2 gene test to provide risk assessment. Subsequently, timely preventive measures for mutation carriers are recommended after authentic genetic counseling.
Identification and validation of a potential key gene SGOL1 for poor prognosis in hepatocellular carcinoma based on a bioinformatics approach
Authors: Fei Xiaobin , Liu Songbai , Liu Peng , Wang Xing , Zhu Changhao , Hou Junyi , Cai Junzhe , Pan Yaozhen
Published: November 2022

Objective

Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. Shugoshin 1 (SGOL1) plays a crucial role in cell mitosis and its aberrant expression level in human tumors has shown to promote chromosomal instability (CIN) and accelerate tumor growth. SGOL1 expression level in HCC cells and tissues, whether it has an influence on HCC patients’ prognosis, and its mechanism of action have not yet been studied.

Methods

We carried out the bioinformatics analysis of SGOL1 expression level and survival analysis in 8 different malignancies, including HCC. In addition, we analyzed SGOL1 expression level in HCC tissues, as well as HCC patients’ clinical features, enrichment analysis of SGOL1 function and mechanism of action in HCC and tumor immune cells. The effects of SGOL1 expression level and cell viability on HCC were confirmed by in vitro cytological assays.

Results

It was found that SGOL1 mRNA expression level was significantly higher in several tumor tissues, including HCC, than in corresponding normal tissues, and the elevated SGOL1 expression level was strongly associated with HCC patients’ poor prognosis. It was also revealed that SGOL1 expression level in HCC tissue was positively correlated with disease stage, tumor grade, and tumor size, and the results of multivariate logistic regression analysis showed that SGOL1 was one of the independent influential factors of the prognosis of HCC. Enrichment analysis revealed that SGOL1 expression level in HCC tissue was mainly associated with tumor proliferation, cell cycle, and other factors. The results of the immune infiltration analysis indicated that SGOL1 expression level was associated with immune cell infiltration and immune checkpoints in HCC. In vitro experiments demonstrated the high SGOL1 expression level in HCC tissues and cells, and silencing of SGOL1 resulted in altered cell cycle markers and decreased proliferation, invasion, and migration of HCC cells.

Conclusion

The findings revealed that SGOL1 is highly expressed in HCC tissues, it is a biomarker of a poor prognosis, which may be related to immune cell infiltration in HCC, and may enhance the proliferation, invasion, and migration of HCC cells. The results may provide new insights into targeted treatment of HCC and improve HCC patients’ prognosis.
Phenolic diterpenes from Rosemary supercritical extract inhibit non-small cell lung cancer lipid metabolism and synergise with therapeutic drugs in the clinic
Authors: Bouzas Adrián , Gómez de Cedrón Marta , Colmenarejo Gonzalo , Laparra-Llopis José Moisés , Moreno-Rubio Juan , Montoya Juan José , Reglero Guillermo , Casado Enrique , Tabares Beatriz , Sereno María , Ramírez de Molina Ana
Published: November 2022

Lung cancer is one of the most deadly and common cancers in the world. The molecular features of patient’s tumours dictate the different therapeutic decisions, which combines targeted therapy, chemotherapy, and immunotherapy. Altered cellular metabolism is one of the hallmarks of cancer. Tumour cells reprogram their metabolism to adapt to their novel requirements of growth, proliferation, and survival. Together with the Warburg effect, the role of lipid metabolism alterations in cancer development and prognosis has been highlighted. Several lipid related genes have been shown to promote transformation and progression of cancer cells and have been proposed as biomarkers for prognosis. Nevertheless, the exact mechanisms of the regulation of lipid metabolism and the biological consequences in non-small cell lung cancer (NSCLC) have not been elucidated yet. There is an urgent necessity to develop multidisciplinary and complementary strategies to improve NSCLC patients´ well-being and treatment response. Nutrients can directly affect fundamental cellular processes and some diet-derived ingredients, bioactive natural compounds and natural extracts have been shown to inhibit the tumour growth in preclinical and clinical trials. Previously, we described a supercritical extract of rosemary (SFRE) (12 - 16% composition of phenolic diterpenes carnosic acid and carnosol) as a potential antitumoral agent in colon and breast cancer due to its effects on the inhibition of lipid metabolism and DNA synthesis, and in the reduction of resistance to 5-FluoroUracil (5-FU). Herein, we demonstrate SFRE inhibits NSCLC cell bioenergetics identifying several lipid metabolism implicated targets. Moreover, SFRE synergises with standard therapeutic drugs used in the clinic, such as cisplatin, pemetrexed and pembrolizumab to inhibit of cell viability of NSCLC cells. Importantly, the clinical relevance of SFRE as a complement in the treatment of NSCLC patients is suggested based on the results of a pilot clinical trial where SFRE formulated with bioactive lipids (PCT/ES2017/070263) diminishes metabolic and inflammatory targets in peripheral-blood mononuclear cells (PBMC), such as MAPK (p=0.04), NLRP3 (p=0.044), and SREBF1 (p=0.047), which may augment the immune antitumour function. Based on these results, SFRE merits further investigation as a co-adjuvant in the treatment of NSCLC.

Clinical trial registration

ClinicalTrials.gov Identifier NCT05080920
Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies
Authors: Nakatsumi Hiroshi , Komatsu Yoshito , Muranaka Tetsuhito , Yuki Satoshi , Kawamoto Yasuyuki , Harada Kazuaki , Dazai Masayoshi , Tateyama Miki , Sasaki Yusuke , Miyagishima Takuto , Tsuji Yasushi , Katagiri Masaki , Nakamura Michio , Sogabe Susumu , Hatanaka Kazuteru , Meguro Takashi , Kobayashi Tomoe , Ishiguro Atsushi , Muto Osamu , Shindo Yoshiaki , Kotaka Masahito , Ando Takayuki , Takagi Ryo , Sakamoto Naoya , Sakata Yu
Published: November 2022

Background

The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies.

Methods

FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi.

Discussion

There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy.

Clinical trial registration

Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis
Authors: Li Yiling , Xiu Lin , Ma Mingyuan , Seery Samuel , Lou Xiaoying , Li Kexin , Wu Yue , Liang Shuang , Wu Yuxin , Cui Wei
Published: November 2022

Purpose

Lymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS).

Methods

1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan–Meier’s and Fine-Gray’s tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms’ performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems.

Results

Multivariate Cox’s regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort.

Conclusions

LODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.
Surgical clinical trials for HPV-positive oropharyngeal carcinoma
Authors: Lin Chen , Sharbel Daniel D. , Topf Michael C.
Published: November 2022

The treatment of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) continues to evolve as multiple ongoing and recently completed clinical trials investigate the role of surgery, radiation therapy, chemotherapy, and immunotherapy. Current trials are investigating transoral robotic surgery (TORS) in treatment de-escalation protocols in an effort to optimize quality of life, while maintaining historical survival rates. The advantage of TORS is its minimally invasive approach to primary resection of the tumor as well as valuable pathologic staging. The ORATOR trial reported poorer quality of life in patients treated with TORS compared to primary radiotherapy though this was not a clinically meaningful difference. The recently published ECOG 3311 trial showed that surgery can be used to safely de-escalate the adjuvant radiation dose to 50 Gy in intermediate-risk patients. In this review, we summarize and discuss the past and current clinical trials involving surgery in the treatment of HPV-positive OPSCC.
NEO-SPEAK: A conceptual framework that underpins breaking bad news in neonatology
Authors: Seifart Carola , Falch Mirjam , Wege Mirjam , Maier Rolf F. , Pedrosa Carrasco Anna J.
Published: November 2022

Objective

Breaking bad news in neonatology is a frequent and difficult challenge. Although there are guidelines for communicating with parents in pediatrics and neonatology, the specific framework for breaking bad news in neonatology has not been studied in more detail. Therefore, we aimed to identify determinants that are important for successful managing breaking bad news in neonatology from professionals' perspective and to develop a conceptual framework that underpins this challenging task.

Methods

We conducted seventeen semi-structured interviews with senior neonatologists of six perinatal centers of the highest level of care in Germany. The transcripts were analyzed according to Mayring's method of qualitative content analysis using inductive and deductive coding.

Results

Eight determinants of breaking bad news in neonatology could be identified from the interviews. From these, we developed the conceptual framework NEO-SPEAK. The first three determinants, Neonatal prognostic uncertainty, Encounter in (triangular-)partnerships, Organization and teamwork (NEO) are directly related to the specific care situation in neonatology, whereas the others, Situational stress, Processuality, Emotional burden, Attention to individuality, Knowledge and experience, play a role for difficult conversations in general, but are subject to special modifications in neonatology (SPEAK). In addition, the results show that the context in neonatology as well as reciprocal effects on the team and the individual level of the physicians are important influencing factors in breaking bad news.

Conclusion

On the one hand, the constitutional framework NEO-SPEAK shows which special aspects play a role in neonatology for the delivery of bad news, and on the other hand, it can help to identify and consider these aspects in clinical routine and training. Considering or reinforcing each NEO-SPEAK element when planning or delivering bad news may guide healthcare professionals through communication with parents of critically ill or premature newborns and support the resilience of the caring team.
The conservative treatment of congenital scoliosis with hemivertebra: Report of three cases
Authors: Caredda Matteo , Bandinelli Diletta , Falciglia Francesco , Giordano Marco , Aulisa Angelo Gabriele
Published: November 2022

Introduction

Scoliosis is the most common type of congenital vertebral disease. This spinal disorder may be due to a failure of formation, segmentation, or a combination thereof. Complete failure of formation causes hemivertebra which can lead to unbalanced growth and deformation. Statistically, 25% of congenital curves do not evolve, 25% progress slightly, while the remaining 50% develop quickly and require treatment. Hemivertebrae can be divided into three types: non-segmented, semi-segmented, and fully-segmented. The fully-segmented types are most likely to progress. Hemivertebra in the thoracolumbar region shows higher rates of progression compared with those in the lumbar area. The treatment may be either conservative or surgical. In general, bracing is not recommended in short and rigid curves, although it may help process secondary curves.

Objective

To assess the effectiveness of bracing in congenital scoliosis due to hemivertebra.

Cases presentation

Searching in our database, we found three cases of patients with congenital scoliosis due to fully-segmented hemivertebra. The first of them was 6 years old at the time of diagnosis with a fully-segmented hemivertebra in L5, determining an L1-L5 (S1) lumbar curve. The second one was 10 years old at the time of diagnosis with a fully-segmented hemivertebra in L2 and a T11-L4 (L5 sacralized) thoracolumbar curve. The last one was 3 years old at the time of diagnosis with a fully-segmented hemivertebra in L3 (in six lumbar bodies), determining a thoracolumbar curve T12-L4.

Results

We utilized a Milwaukee brace for the first patient, a Boston brace for the second patient, and a Progressive Action Short Brace (PASB) for the third patient. At the beginning of the treatment, the Cobb angles measured 23°, 53°, and 25°, respectively. During treatment, the Cobb angles measured 22°, 35°, and 15°, respectively. At the end of treatment, the Cobb angles measured 18°, 45°, and 12°, respectively. At long-term follow-up, the curves measured 20°, 45°, and 12° Cobb angles, respectively.

Conclusions

Comparing our cases with those found in the literature we can confirm the ability of conservative treatment to change the natural history of congenital lumbar scoliosis due to failure of formation. From our experience, in all cases of CS with hemivertebra, before considering a surgical approach, conservative treatment should be implemented as early as possible without waiting for the progressive deformation of the adjacent normal vertebrae.
Institutionalizing health technology assessment in Egypt: Situational analysis and roadmap
Authors: Pinilla-Dominguez Pilar , Taha Shorouk , McGuire Hugh , Elagamy Ahmed , Sedrak Amal , Gamal Mary , Eldebeiky Mariam , Dawoud Dalia
Published: November 2022

Objective: To conduct a situational analysis with the aim to inform future health technology assessment efforts (HTA) in Egypt.

Introduction: The Egyptian government has set universal health coverage as a 2030 target. Several agencies have been created in the context of the ongoing healthcare reform. The Egyptian Authority for Unified Procurement, Medical Supply and the Management of Medical Technology (UPA) is one of them and was established to support strategic procurement using HTA.

Methods: Description of the development of HTA in Egypt supported by a literature search as part of a scoping exercise, and a stakeholder analysis and identification of HTA capacity survey, based on previous surveys, with relevant stakeholders conducted in 2022. This was followed by a stakeholder event where results were shared and further contextualized.

Results: The UPA is expected to evaluate the cost-effectiveness of health technologies and public health programs. The HTA process is being developed, focusing on the assessment of the value of new pharmaceuticals being introduced to the Egyptian market. A total of 16 participants responded on behalf of their organizations to the stakeholder analysis and identification of HTA capacity survey. More than 80% of the respondents were familiar with current efforts conducted by UPA and strongly support the implementation of HTA in Egypt. Transparency was highlighted as an important criterion. Over 90% of the respondents mentioned economic analyses as an HTA product being developed in Egypt, and medicines were the type of technology that stakeholders ranked as first in the rank of health technologies that need the output from HTA urgently. Capability building and training were highlighted as areas in which further support is required.

Conclusion: This study represents the first attempt to describe the current path for HTA in Egypt. There seems to be momentum in Egypt to proceed and advance with HTA institutionalization. It would be important that next steps are built on the skills and capabilities already in place in Egypt, ensure methods and processes are in place and up to date and involve the wider system in Egypt so stakeholders can appropriately contribute and participate in the HTA process.