bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-Differences and Associations Between Complement Activation and Synovial Vascularization in Patients with Late-Stage Knee Osteoarthritis
Authors: Sodhi Emily U. , Philpott Holly T. , Carter McKenzie M. , Birmingham Trevor B. , Appleton C. Thomas
Published: May 2022

Purpose

Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and synovial microvascular pathology have not been established. Since complement causes vascular pathology in other diseases and since sex-differences exist in complement activation and in OA, we investigated sex differences in synovial fluid complement factors, synovial tissue vascular pathology, and associations between complement and synovial vascular pathology in patients with late-stage knee OA.

Methods

Patients with symptomatic, late-stage radiographic knee OA undergoing total knee arthroplasty or high tibial osteotomy provided matched synovial fluid and tissue biopsies during surgery. Complement factors (C2, C5, adipsin, MBL, and CFI) and terminal complement complex (sC5b-C9) were measured in synovial fluid by multiplex or enzyme-linked immunosorbent assay, respectively. Features of synovial vascular pathology (vascularization, perivascular edema, and vasculopathy) were assessed by histopathology. Multivariate linear regression models were used to assess associations between synovial fluid complement factors and histopathological features of vascular pathology, with adjustment for age, sex, body mass index, and sex interaction. Sex-disaggregated comparisons were completed.

Results

Synovial fluid biomarker and histopathology data were included from 97 patients. Most synovial fluid complement factors and synovial tissue histopathological features were similar between sexes. Synovial fluid C5 trended to lower levels in males (-20.93 ng/mL [95%CI -42.08, 0.23] p=0.05). Median vasculopathy scores (0.42 [95%CI 0.07, 0.77] p=0.02) were higher in males. In the full cohort, C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.010, -0.0001] p=0.04) while accounting for sex*C5 interaction. In sex-disaggregated analyses, increased C5 concentration was associated with lower vascularization scores (-0.005 [95%CI –0.009, -0.0001] p=0.04) in male patients, but not in female patients. Males had higher sC5b-C9 compared to females. Additionally, males with high C5 had a higher synovial fluid concentration of sC5b-C9 compared to males with low C5. No differences were found in females.

Conclusion

Higher synovial fluid C5 levels were associated with increased complement activation and decreased synovial vascularization in males but not in females with OA. Future studies should test whether synovial fluid complement activation suppresses synovial angiogenesis and identify mechanisms accounting for C5-related sex-differences in synovial fluid complement activation in patients with knee OA.
Primary Graft Dysfunction: The Role of Aging in Lung Ischemia-Reperfusion Injury
Authors: Roesel Maximilian J. , Sharma Nirmal S. , Schroeter Andreas , Matsunaga Tomohisa , Xiao Yao , Zhou Hao , Tullius Stefan G.
Published: May 2022

Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population, older donors are increasingly considered. Donor age, at the same time has been linked to higher rates of lung ischemia reperfusion injury (IRI). This process of acute, sterile inflammation occurring upon reperfusion is a key driver of primary graft dysfunction (PGD) leading to inferior short- and long-term survival. Understanding and improving the condition of older lungs is thus critical to optimize outcomes. Notably, ex vivo lung perfusion (EVLP) seems to have the potential of reconditioning ischemic lungs through ex-vivo perfusing and ventilation. Here, we aim to delineate mechanisms driving lung IRI and review both experimental and clinical data on the effects of aging in augmenting the consequences of IRI and PGD in lung transplantation.
Salvage Endoscopic Skull Base Surgery: Another Treatment Option After Immunotherapy for Recurrent Nasopharyngeal Carcinoma
Authors: Peng Zhouying , Wang Yumin , Fang Yan , Wang Yaxuan , Yuan Xiaotian , Shuai Mingxia , Xie Shumin , Fan Ruohao , Zhang Hua , Xie Zhihai , Jiang Weihong
Published: May 2022

Background

Advanced recurrent nasopharyngeal carcinoma (NPC) is a relatively common nasopharyngeal skull base disease for which there is no uniform treatment modality. Not all patients are satisfied with the efficacy of immunotherapy with or without chemotherapy.

Methods

This study included patients who underwent salvage endoscopic skull base nasopharyngectomy after immunotherapy between February 2017 and June 2021. Patient survival information was analyzed. Relevant publications were retrieved from five databases from December 1, 2011 to December 1, 2021. The outcomes of patients with advanced recurrent NPC who received programmed death 1 (PD-1) immunotherapy were collected and analyzed.

Results

Nine patients who underwent skull base surgery, all of whom had previously undergone PD-1 immunotherapy, were included in this study. The 2-year overall survival (OS) and progression-free survival (PFS) rates of these patients were 25% and 29.2%, respectively. Eight publications involving 688 patients with advanced recurrent NPC were also included in this study. The combined complete response (CR), partial response (PR), and stable disease (SD) values were 2%, 23%, and 29%, respectively. The combined DCR included the three disease conditions, CR, PR, and SD, with a value of 53%. PD-1 monotherapy was more effective than PD-1 combination chemotherapy.

Conclusions

PD-1 immunotherapy may improve the remission rate in patients with recurrent NPC. Salvage endoscopic skull base nasopharyngectomy may be another option for patients with poor immunotherapeutic outcomes. For patients with advanced recurrent NPC, better evidence-based medical data are needed to determine whether they should receive immunotherapy before or after surgery.
Quaternary Ammonium Compounds as Candidate Photoprotective Compounds in Reef-Building Corals
Authors: Hill Richard W.
Published: May 2022

Quaternary ammonium compounds (QACs) – e.g., betaines – have a chemical structure related to that of the tertiary sulfonium compounds (TSCs) – e.g., dimethylsulfoniopropionate – explaining why these two classes of coral metabolites are often studied and interpreted together. Functionally, both QACs and TSCs play important roles in the photobiology of reef-building corals under stress, according to recent hypotheses. The TSC dimethylsulfoniopropionate (DMSP) is the principal precursor of the gas dimethylsulfide (DMS) which is hypothesized to affect, through influences on cloud formation, the photon and thermal fluxes to which corals are exposed. Simultaneously, QACs – e.g., glycine betaine – in coral tissues are hypothesized to protect the zooxanthellae photosystems against photon and thermal stresses by exerting stabilizing effects on photosystem proteins and by ameliorating reactive-oxygen-species perturbations. This review, which synthesizes the most current available evidence on the relevant actions of QACs, emphasizes the need for enhanced direct study of QAC physiology in corals to ascertain the degree to which coral QACs exert photoprotective effects paralleling their well-established protective effects in plants.
Gelatinous Carbon Impacts Benthic Megafaunal Communities in a Continental Margin
Authors: Lebrato Mario , Molinero Juan-Carlos , Mychek-Londer Justin G. , Gonzalez Elena Mateo , Jones Daniel O. B.
Published: May 2022

Post-collapse of seasonal blooms of gelatinous zooplankton (Cnidaria, Ctenophora, and Thaliacea) sinking carcasses transports labile carbon (jelly-C) to benthic continental margins and the deep sea. In recent decades, bloom frequency and intensity have increased globally; however, how sinking jelly-C affects benthic communities is poorly known. Further, as climate change and other anthropogenic impacts may increase gelatinous blooms in the future, understanding the contributions and impacts of jelly-C upon benthic communities is of pivotal importance. Thus, in this study, we assessed jelly-C deposits post-intense blooming of a pelagic species of marine colonial gelatinous tunicate in the Thaliacean class, Pyrosoma atlanticum. We studied the seabed using a remotely operated vehicle (ROV) from 26 to 1,276 m, documenting jelly-C deposits and species of the megafaunal benthic community. Environmental variables from water column profiles at transects near our own off the Ivory Coast of West Africa were used in assessments. Jelly-C biomass peaked at 400 m (1,500 grC 100 m−2) and remained at the average (300 grC 100 m−2) through 1,276 m. Typically, in depth strata between 300 and 800 m, peaks in jelly-C biomass (500 to 1,500 grC 100 m−2) corresponded to areas with significantly reduced benthic megafaunal species abundances as well as diversity. From 800 to 1,276 m, we noted patchier jelly-C biomass deposits where individual megafauna species abundances and diversity correspondingly increased, yet total organism counts remained low. We observed 11 species from 5 phyla directly feeding on jelly-C and 10 single-species aggregations triggering megafaunal dominance events at various localized depth strata. Although such dynamics have been hypothesized and examined for some time with respect to phytodetritus biomass, they have been rarely described for jelly-C. Thus, our novel findings for jelly-C dynamics in the offshore regions can help to provide a better understanding of the ecological role that this component plays in marine benthic ecosystems and continental margins.
Lessons From Insect Fungiculture: From Microbial Ecology to Plastics Degradation
Authors: Barcoto Mariana O. , Rodrigues Andre
Published: May 2022

Anthropogenic activities have extensively transformed the biosphere by extracting and disposing of resources, crossing boundaries of planetary threat while causing a global crisis of waste overload. Despite fundamental differences regarding structure and recalcitrance, lignocellulose and plastic polymers share physical-chemical properties to some extent, that include carbon skeletons with similar chemical bonds, hydrophobic properties, amorphous and crystalline regions. Microbial strategies for metabolizing recalcitrant polymers have been selected and optimized through evolution, thus understanding natural processes for lignocellulose modification could aid the challenge of dealing with the recalcitrant human-made polymers spread worldwide. We propose to look for inspiration in the charismatic fungal-growing insects to understand multipartite degradation of plant polymers. Independently evolved in diverse insect lineages, fungiculture embraces passive or active fungal cultivation for food, protection, and structural purposes. We consider there is much to learn from these symbioses, in special from the community-level degradation of recalcitrant biomass and defensive metabolites. Microbial plant-degrading systems at the core of insect fungicultures could be promising candidates for degrading synthetic plastics. Here, we first compare the degradation of lignocellulose and plastic polymers, with emphasis in the overlapping microbial players and enzymatic activities between these processes. Second, we review the literature on diverse insect fungiculture systems, focusing on features that, while supporting insects’ ecology and evolution, could also be applied in biotechnological processes. Third, taking lessons from these microbial communities, we suggest multidisciplinary strategies to identify microbial degraders, degrading enzymes and pathways, as well as microbial interactions and interdependencies. Spanning from multiomics to spectroscopy, microscopy, stable isotopes probing, enrichment microcosmos, and synthetic communities, these strategies would allow for a systemic understanding of the fungiculture ecology, driving to application possibilities. Detailing how the metabolic landscape is entangled to achieve ecological success could inspire sustainable efforts for mitigating the current environmental crisis.
Prevalence, Cell Tropism, and Clinical Impact of Human Parvovirus Persistence in Adenomatous, Cancerous, Inflamed, and Healthy Intestinal Mucosa
Authors: Xu Man , Leskinen Katarzyna , Gritti Tommaso , Groma Valerija , Arola Johanna , Lepistö Anna , Sipponen Taina , Saavalainen Päivi , Söderlund-Venermo Maria
Published: May 2022

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.
Time-Varying Effective Connectivity for Describing the Dynamic Brain Networks of Post-stroke Rehabilitation
Authors: Xu Fangzhou , Wang Yuandong , Li Han , Yu Xin , Wang Chongfeng , Liu Ming , Jiang Lin , Feng Chao , Li Jianfei , Wang Dezheng , Yan Zhiguo , Zhang Yang , Leng Jiancai
Published: May 2022

Hemiplegia is a common motor dysfunction caused by a stroke. However, the dynamic network mechanism of brain processing information in post-stroke hemiplegic patients has not been revealed when performing motor imagery (MI) tasks. We acquire electroencephalography (EEG) data from healthy subjects and post-stroke hemiplegic patients and use the Fugl-Meyer assessment (FMA) to assess the degree of motor function damage in stroke patients. Time-varying MI networks are constructed using the adaptive directed transfer function (ADTF) method to explore the dynamic network mechanism of MI in post-stroke hemiplegic patients. Finally, correlation analysis has been conducted to study potential relationships between global efficiency and FMA scores. The performance of our proposed method has shown that the brain network pattern of stroke patients does not significantly change from laterality to bilateral symmetry when performing MI recognition. The main change is that the contralateral motor areas of the brain damage and the effective connection between the frontal lobe and the non-motor areas are enhanced, to compensate for motor dysfunction in stroke patients. We also find that there is a correlation between FMA scores and global efficiency. These findings help us better understand the dynamic brain network of patients with post-stroke when processing MI information. The network properties may provide a reliable biomarker for the objective evaluation of the functional rehabilitation diagnosis of stroke patients.
Ketogenic Diet Therapy for Drug-Resistant Epilepsy and Cognitive Impairment in Children With Tuberous Sclerosis Complex
Authors: Fang Yu , Li Dan , Wang Man , Zhao Xia , Duan Jing , Gu Qiang , Li Baomin , Zha Jian , Mei Daoqi , Bian Guangbo , Zhang Man , Zhang Huiting , Hu Junjie , Yang Liu , Yu Lifei , Li Hua , Liao Jianxiang
Published: May 2022

Objective

Tuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC.

Methods

In this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy.

Results

Of the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment.

Conclusion

KD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.
Brain Activity in Different Brain Areas of Patients With Dry Eye During the Female Climacteric Period According to Voxel-Based Morphometry
Authors: Hu Meng-Yan , Zhang Li-Juan , Kang Min , Pan Yi-Cong , Ge Qian-min , Li Qiu-yu , Yang Lin , Pei Chong-Gang , Shao Yi
Published: May 2022

We aim to investigate potential morphological alterations of the brain in female climacteric patients with dry eye (DE) and their relationship to behavioral performances. Twenty-five female patients with DE disease during the female climacteric period and 25 age and education-matched healthy controls (HCs) underwent magnetic resonance imaging. Imaging data were analyzed using voxel-based morphometry (VBM) to identify group differences in DE patients and HCs. Compared with HCs, patients with DE during the female climacteric period had significantly decreased VBM in the Putamen_L, Thalamus_R, Precuneus_L, Frontal_Sup_R, Cingulum_Mid_L, and Frontal_Mid_L. There was increased VBM in the Temporal_Pole_Sup_R, Precentral_R and Insula_L. Receiver operating characteristic curve analysis indicated that the VBM method has clear potential for diagnosis of DE patients during the climacteric period. Correlation analysis found a negative correlation between the VBM values of the Putamen_L and the anxiety score (AS) and depression score (DS), a positive correlation was found between VBM values of the Temporal_Pole_Sup_R and AS. Moreover, VBM values in the Cingulum_Mid_L were positively correlated with AS and DS. These results revealed abnormal spontaneous activity in the brain regions of patients with DE during the climacteric period, which may indicate underlying pathological mechanisms. These results may help to advance clinical treatments.
Effects of Vascular Comorbidity on Cognition in Multiple Sclerosis Are Partially Mediated by Changes in Brain Structure
Authors: Marrie Ruth Ann , Patel Ronak , Figley Chase R. , Kornelsen Jennifer , Bolton James M. , Graff Lesley A. , Mazerolle Erin L. , Helmick Carl , Uddin Md Nasir , Figley Teresa D. , Marriott James J. , Bernstein Charles N. , Fisk John D.
Published: May 2022

Objective

Vascular comorbidities are associated with reduced cognitive performance and with changes in brain structure in people with multiple sclerosis (MS). Understanding causal pathways is necessary to support the design of interventions to mitigate the impacts of comorbidities, and to monitor their effectiveness. We assessed the inter-relationships among vascular comorbidity, cognition and brain structure in people with MS.

Methods

Adults with neurologist-confirmed MS reported comorbidities, and underwent assessment of their blood pressure, HbA1c, and cognitive functioning (i.e., Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, and verbal fluency). Test scores were converted to age-, sex-, and education-adjusted z-scores. Whole brain magnetic resonance imaging (MRI) was completed, from which measures of thalamic and hippocampal volumes, and mean diffusivity of gray matter and normal-appearing white matter were converted to age and sex-adjusted z-scores. Canonical correlation analysis was used to identify linear combinations of cognitive measures (cognitive variate) and MRI measures (MRI variate) that accounted for the most correlation between the cognitive and MRI measures. Regression analyses were used to test whether MRI measures mediated the relationships between the number of vascular comorbidities and cognition measures.

Results

Of 105 participants, most were women (84.8%) with a mean (SD) age of 51.8 (12.8) years and age of symptom onset of 29.4 (10.5) years. Vascular comorbidity was common, with 35.2% of participants reporting one, 15.2% reporting two, and 8.6% reporting three or more. Canonical correlation analysis of the cognitive and MRI variables identified one pair of variates (Pillai's trace = 0.45, p = 0.0035). The biggest contributors to the cognitive variate were the SDMT and CVLT-II, and to the MRI variate were gray matter MD and thalamic volume. The correlation between cognitive and MRI variates was 0.50; these variates were used in regression analyses. On regression analysis, vascular comorbidity was associated with the MRI variate, and with the cognitive variate. After adjusting for the MRI variate, vascular comorbidity was not associated with the cognitive variate.

Conclusion

Vascular comorbidity is associated with lower cognitive function in people with MS and this association is partially mediated via changes in brain macrostructure and microstructure.
Association Between Healthy Eating Index-2015 and Kidney Stones in American Adults: A Cross-Sectional Analysis of NHANES 2007–2018
Authors: Yin Shan , Wang Jiahao , Bai Yunjin , Yang Zhenzhen , Cui Jianwei , Xiao Yunfei , Wang Jia
Published: May 2022

Purpose

To explore the association between Healthy Eating Index (HEI)-2015 and kidney stones in an American adult population.

Materials and Methods

National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 were used. Participants aged ≥ 20 years who reported kidney stone history and dietary recall were included. Weighted proportions, multivariable analysis and spline smoothing were used to evaluate the associations between HEI-2015 and nephrolithiasis by adjusting gender, age, race, poverty income ratio, body mass index, education level, marital status, smoking, alcohol intake, energy level, vigorous activity, moderate activity, and some comorbidities.

Results

Totally 30 368 American adults were included, with weighted mean age [standard deviation (SD)] of 47.69 (16.85) years. The overall mean HEI-2015 score (SD) was 50.82 (13.80). In the fully-adjusted multivariable model, HEI-2015 was negatively correlated with urolithiasis [odds ratio (OR) = 0.991; 95% confidence interval (CI) 0.988 to 0.994]. Compared with the first quartile of HEI-2015, the population in the fourth quartile of HEI-2015 had a lower prevalence of kidney stones (OR = 0.716; 95% CI 0.635 to 0.807). The association was modified by education and vigorous activity.

Conclusions

HEI-2015 is inversely associated with the prevalence of kidney stones, which means better diet quality is associated with a lower risk of nephrolithiasis.
Ferulic Acid Treatment Maintains the Quality of Fresh-Cut Taro (Colocasia esculenta) During Cold Storage
Authors: Wang Bin , Huang Yongyan , Zhang Zhenming , Xiao Yanhui , Xie Jing
Published: May 2022

Taro (Colocasia esculenta) is a major root crop or vegetable in the world, and the corm is a good source of many nutrients including starch, vitamins, and minerals. Taro corms are processed into various forms before consumption, which makes them perishable, reduces the shelf life, and increases postharvest losses. The surface browning of fresh-cut taros is one of the major factors that limits storage life and affects consumer acceptance. In this study, the effects of ferulic acid (FA) as an effective agent in the prevention of quality deterioration were investigated. Fresh-cut taros were immersed in distilled water and different concentrations of FA (1, 2, 5, 10, and 20 mM) solutions for 30 min, air-dried at 25°C for 30 min, and then stored at 5°C for 12 days to investigate the effects of FA on browning. Among the FA concentrations tested, 10 mM resulted in significantly higher L* values, lower a* and b*, and browning index values. FA treatment (10 mM) also induced de novo biosynthesis of two volatile compounds, including non-anal and octanoic acid ethyl ester in fresh-cut taros following extended cold storage. The results suggest that FA treatment maintains the quality of fresh-cut taros under cold conditions. FA treatment enhanced PAL activity and gene expression but reduced total phenolic content and the expression of six C4H, 4CL, and CHS genes, suggesting that FA treatment reduced phenolic biosynthesis. FA treatment reduced PPO activity and gene expression and decreased soluble quinone content, suggesting that FA treatment suppressed the phenolic oxidation. FA treatment enhanced the activity and gene expression of CAT and POD, reduced those of LOX, and decreased MDA and H2O2 levels, suggesting that FA treatment activated the antioxidant defense system and thereby reduced oxidative damage. These findings demonstrated that FA treatment could serve as an effective approach to retard the browning of fresh-cut taros and provided a basis for the feasible application of FA in the preservation of fresh-cut foods.
Sphingomyelin Phodiesterase Acid-Like 3A Promotes Hepatocellular Carcinoma Growth Through the Enhancer of Rudimentary Homolog
Authors: Zhang Yu , Chen Weipeng , Cheng Xin , Wang Feiran , Gao Cheng , Song Fei , Song Fengliang , Liang Xiaoliang , Fang Wanzhi , Chen Zhong
Published: May 2022

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with unclear pathogenesis. Sphingomyelin phodiesterase acid-like 3A (SMPDL3A) affects cell differentiation and participates in immune regulation. However, its molecular biological function in HCC has not yet been elucidated.

Methods

Data from 180 HCC patients were analyzed the relationship between the expression of SMPDL3A in liver cancer tissues and the prognosis of liver cancer patients. Crispr-Cas9 dual vector lentivirus was used to knock out SMPDL3A in HCC cell lines. The effects of SMPDL3A on cell viability were determined by CCK8 assay, clone formation experiment, cell cycle assay, cell scratch, TUNEL experiment and flow cytometry. Xenograft tumor assays in BALB/c nude mice confirmed that SMPDL3A promoted tumor growth and in vivo. Preliminary exploration of SMPDL3A interacting protein by mass spectrometry analysis and co-immunoprecipitation.

Results

This study showed that the expression of SMPDL3A in HCC tissue differed from that in tumor-adjacent tissues. Moreover, the overall survival rate and tumor-free survival rate of patients with high-SMPDL3A expression were significantly lower than those with low-SMPDL3A expression. SMPDL3A expression was closely related to the level of protein induced by PIVKA-II, liver cirrhosis, tumor diameter, microvascular invasion, and Barcelona clinic liver cancer staging. Thus, SMPDL3A is an independent risk factor that affects the tumor-free survival rate and overall survival rate of HCC patients. In vitro study using Crispr-Cas9 genome editing technology revealed the knockout effect of SMPDL3A on cell proliferation, apoptosis, and migration. Cell counting kit-8 assay and clone formation experiment showed that sgSMPDL3A inhibited tumor cell proliferation and migration. Flow cytometry and TUNEL assay showed that sgSMPDL3A promoted apoptosis in tumors. Moreover, sgSMPDL3A inhibited tumor growth during subcutaneous tumor formation in nude mice. Immunohistochemistry of Ki67 and PNCA also indicated that sgSMPDL3A inhibited subcutaneous tumor proliferation in tumor-bearing nude mice. Further experiments showed that SMPDL3A interacts with the enhancer of rudimentary homolog (ERH).

Conclusions

High-SMPDL3A expression was related to poor prognosis of patients with HCC. Knockout of SMPDL3A inhibited the proliferation and migration and accelerated the migration of HCC cells. SMPDL3A interacted with ERH to affect the tumorigenesis and progression of HCC.
Extracellular Vesicles: A New Source of Biomarkers in Pediatric Solid Tumors? A Systematic Review
Authors: Lak Nathalie S. M. , van der Kooi Elvera J. , Enciso-Martinez Agustin , Lozano-Andrés Estefanía , Otto Cees , Wauben Marca H. M. , Tytgat Godelieve A. M.
Published: May 2022

Virtually every cell in the body releases extracellular vesicles (EVs), the contents of which can provide a “fingerprint” of their cellular origin. EVs are present in all bodily fluids and can be obtained using minimally invasive techniques. Thus, EVs can provide a promising source of diagnostic, prognostic, and predictive biomarkers, particularly in the context of cancer. Despite advances using EVs as biomarkers in adult cancers, little is known regarding their use in pediatric cancers. In this review, we provide an overview of published clinical and in vitro studies in order to assess the potential of using EV-derived biomarkers in pediatric solid tumors. We performed a systematic literature search, which yielded studies regarding desmoplastic small round cell tumor, hepatoblastoma, neuroblastoma, osteosarcoma, and rhabdomyosarcoma. We then determined the extent to which the in vivo findings are supported by in vitro data, and vice versa. We also critically evaluated the clinical studies using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system, and we evaluated the purification and characterization of EVs in both the in vivo and in vitro studies in accordance with MISEV guidelines, yielding EV-TRACK and PedEV scores. We found that several studies identified similar miRNAs in overlapping and distinct tumor entities, indicating the potential for EV-derived biomarkers. However, most studies regarding EV-based biomarkers in pediatric solid tumors lack a standardized system of reporting their EV purification and characterization methods, as well as validation in an independent cohort, which are needed in order to bring EV-based biomarkers to the clinic.
What Is the Most Suitable Agent Combined With Apatinib for Transarterial Chemoembolization Treatment in Advanced Hepatocellular Carcinoma Patients? A Systematic Review and Network Meta-analysis
Authors: Hui Fuhai , Xu Chang , Xu Xiangbo , Chen Jiangxia , Geng Hefeng , Yang Chao , Zhang Yingshi
Published: May 2022

Purpose

Combined therapy with transarterial chemoembolization (TACE) and apatinib is superior in therapeutic effect compared with TACE alone in patients with hepatocellular carcinoma (HCC). To determine the most suitable agent combined with apatinib for TACE treatment, we did a systematic review and network meta-analysis.

Methods

Four electronic databases were searched from inception until November 2021. Randomized controlled trials (RCTs) and retrospective studies that combined therapy of TACE and apatinib (TACE+A) compared with TACE alone were included. We performed random-effect pairwise and network meta-analyses to summarize the outcomes about efficacy and safety.

Results

Forty-five original studies including 3,876 patients were included. In terms of efficacy, we evaluated treatment response, 6 months overall survival (OS), 1 year OS, 6 months progression-free survival (PFS), 1 year PFS, alphafetoprotein (AFP), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF). Significant differences always appear in TACE agent subgroups of adriamycin, platinum, and fluorouracil from both pairwise and network meta-analysis, while significant differences could also be found in apatinib dosage of 500 and >500 mg/day subgroups and in both RCT and retrospective study subgroups. From second time network analysis, compared with TACE alone, subgroups with TACE agents of oxaliplatin, cisplatin, pirarubicin, epirubicin, and 5-fluorouracil ranked front. In addition, the safety of adriamycin, platinum, and fluorouracil subgroups is acceptable.

Conclusions

In conclusion, the most suitable agents in TACE combined with apatinib were adriamycin+platinum ± fluorouracil combination therapy.

Systematic Review Registration

The study was registered with https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311650, PROSPERO, CRD4202022311650
Case Report: Male Lobular Breast Cancer in Hereditary Cancer Syndromes
Authors: Carnevali Ileana , Tedaldi Gianluca , Pensotti Valeria , Sahnane Nora , Micello Donata , Rovera Francesca , Sessa Fausto , Tibiletti Maria Grazia
Published: May 2022

Background

Lobular breast carcinoma (LBC) is considered an exceptionally rare disease in men, including only 1% of all male breast malignancies. The majority of LBCs have negative immunohistochemical staining for E-cadherin (CDH1) expression, and the loss of CDH1 function was traditionally implicated in the tumorigenesis of diffuse gastric cancer as well as LBC. It is well recognized that LBC in women could be involved in both hereditary breast and ovarian cancer (HBOC) and hereditary diffuse gastric cancer (HDGC) syndromes; however, there are no data present in literature about the involvement of male LBC in these inherited conditions.

Methods

BRCA1, BRCA2, and CDH1 genes were performed on DNA from peripheral blood using next-generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification analyses. BRCA2 and CDH1 somatic gene analyses were performed on breast tumoral DNA using the NGS sequencing approach.

Results and conclusions

Here, we describe two men affected by LBC, the carriers of a pathogenic variant of BRCA2 and CDH1 genes, respectively. Our data, including somatic and germline results, demonstrate a strong relationship between male LBC and HBOC/HDGC syndromes, excluding a sporadic origin of LBC in these two patients. Male LBC could represent a sentinel cancer for inherited syndrome identification, and early identification of cancer susceptibility could improve cancer prevention both for men and women in these families. The history of the LBC patient carrier of the CDH1 variant suggests to include male LBC genetic testing criteria and male breast surveillance in HDGC guidelines.
A High Throughput Cell-Based Screen Assay for LINE-1 ORF1p Expression Inhibitors Using the In-Cell Western Technique
Authors: Kou Yanni , Wang Shujie , Ma Yanjie , Zhang Ning , Zhang Zixiong , Liu Qian , Mao Yang , Zhou Rui , Yi Dongrong , Ma Ling , Zhang Yongxin , Li Quanjie , Wang Jing , Wang Jinhui , Zhou Xile , He Chunnian , Ding Jiwei , Cen Shan , Li Xiaoyu
Published: May 2022

Long interspersed nuclear element 1 (LINE-1) is a dominant autonomous retrotransposon in human genomes which plays a role in affecting the structure and function of somatic genomes, resulting in human disorders including genetic disease and cancer. LINE-1 encoded ORF1p protein which possesses RNA-binding and nucleic acid chaperone activity, and interacts with LINE-1 RNA to form a ribonucleoprotein particle (RNP). ORF1p can be detected in many kinds of tumors and its overexpression has been regarded as a hallmark of histologically aggressive cancers. In this study, we developed an In-Cell Western (ICW) assay in T47D cells to screen the compounds which can decrease the expression of ORF1p. Using this assay, we screened 1,947 compounds from the natural products library of Target Mol and Selleckchem, among which three compounds, Hydroxyprogesterone, 2,2':5′,2″-Terthiophene and Ethynyl estradiol displayed potency in diminishing LINE-1 ORF1p expression level. Further mechanistic studies indicated the compounds act by affecting LINE-1 RNA transcription. Notably, we demonstrated that the compounds have an inhibitory effect on the proliferation of several lung and breast cancer cell lines. Taken together, we established a high throughput screening system for ORF1p expression inhibitors and the identified compounds provide some clues to the development of a novel anti-tumor therapeutic strategy by targeting ORF1p.
E-Cigarette Usage and Arthritis in the United States, a Nationwide Cross-Sectional Survey
Authors: Tian Yi , Jiao Zhihua , Mao Yingying , Zhang Zhenyu
Published: May 2022

Aim: The prevalence of the use of electronic cigarettes (e-cigarettes) has grown rapidly in the past decade in the United States. While numerous studies have demonstrated combustible cigarette is closely associated with an increased risk of arthritis diseases, little is known about the effect of e-cigarette usage on inflammatory arthritis diseases. We aimed to determinate if e-cigarette usage is associated with an increased risk of inflammatory arthritis.

Methods: Data were obtained from the Behavioral Risk Factor Surveillance System, which is the largest national telephone-based survey of randomly sampled adults in the United States. A total of 924,882 participants with information on e-cigarette usage and inflammatory arthritis were included. We used multivariable logistic regression to estimate the risk of arthritis associated with e-cigarette usage.

Results: Of the 924,882 participants, there were 30,569 (3.3%) current e-cigarette users, and 314,190 (25.9%) reported to have inflammatory arthritis diseases. In the fully adjusted model, we observed that the odds ratio (OR) (95% confidence interval) of inflammatory arthritis diseases was 1.81 (95% CI, 1.70-1.93) for current e-cigarette users compared with never e-cigarette users. The ORs of inflammatory arthritis diseases were 1.31 (95% CI, 1.18-1.47), and 1.55 (95% CI, 1.42-1.69) among sole e-cigarette and dual users compared with never e-cigarette users, respectively.

Conclusions: This is the first study to observe a cross-sectional association between e-cigarette usage and inflammatory arthritis diseases, and the findings were consistent in both sole-e-cigarette users and dual users. Our findings provide evidence that e-cigarette usage might be an important risk factor for arthritis diseases, which may have regulatory implications for e-cigarette control.
Prediction of Aortic Stenosis Progression by 18F-FDG and 18F-NaF PET/CT in Different Aortic Valve Phenotypes
Authors: Murtazalieva Patimat , Ryzhkova Darya , Malev Eduard , Zhiduleva Ekaterina , Moiseeva Olga
Published: May 2022

Background: Different imaging techniques, such as echocardiography (ECHO) and CT, allow to assess aortic stenosis (AS) severity and could be used to study its progression. But only PET/CT open opportunities to assess activity of valvular inflammation and calcification in vivo. The aim of this study was to assess prognostic value of valvular inflammation and calcification measured by 18F-FDG and 18F-NaF PET/CT in patients with tricuspid (TAV) and bicuspid aortic valve (BAV).

Methods: The study included 71 patients aged 40–70 years with mild, moderate and severe asymptomatic calcific AS. Patients were divided into two groups according to valve morphology: with BAV and TAV. All patients underwent standard ECHO, CT calcium scoring PET/CT with 18F-NaF and 18F-FDG. All patients were evaluated during a follow-up visit with evaluation of ECHO parameters. (16.8 ± 4.2 months).

Results: TAV and BAV groups were comparable in AS severity by ECHO (peak aortic jet velocity (Vmax): 2.90 [2.60; 3.50] vs. 2.96 [2.55; 3.31] m/s, p = 0.83). TBR max 18F-FDG did not vary in TAV and BAV patients (1.15 [1.06; 1.23] vs. 1.11 [1.03; 1.20], p = 0.39). Both groups did not differ in valvular calcification degree (Agatston score 1,058 [440; 1798] vs. 1,128 [533; 2,360], p = 0.55) and calcification activity assessed by 18F-NaF uptake level (TBR max 1.50 [1.30; 1.78] vs. 1.48 [1.27; 1.83], p = 0.97). 18F-NaF TBR max was associated with AS severity measured by Vmax in men and women with TAV (r = 0.54; p = 0.04 vs. r = 0.53; p = 0.03). In BAV group this relationship was true only in female patients (r = 0.1; p = 0.67 vs. r = 0.7; p = 0.0004). There was no association between Vmax and TBR max 18F-FDG was revealed in TAV and BAV groups. During follow-up period, the most important positive predictors of AS progression in TAV obtained by multinomial logistic regression analysis were Vmax, and 18F-NaF TBR. Whereas in BAV the highest predictive value showed model included age and Vmax.

Conclusion:18F-NaF PET/CT may be considered as the valuable predictor for hemodynamic progression of calcific AS in case of TAV. 18F-FDG PET/CT does not play a significant role to predict the AS progression.
A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies
Authors: Fallah Hamideh P , Ahuja Ekta , Lin Haoquan , Qi Jinlong , He Qian , Gao Shan , An Hailong , Zhang Jian , Xie Yongzhen , Liang Dong
Published: May 2022

Transient receptor potential (TRP) proteins are a large group of ion channels that control many physiological functions in our body. These channels are considered potential therapeutic drug targets for various diseases such as neurological disorders, cancers, cardiovascular disease, and many more. The Nobel Prize in Physiology/Medicine in the year 2021 was awarded to two scientists for the discovery of TRP and PIEZO ion channels. Improving our knowledge of technologies for their study is essential. In the present study, we reviewed the role of TRP channel types in the control of normal physiological functions as well as disease conditions. Also, we discussed the current and novel technologies that can be used to study these channels successfully. As such, Flux assays for detecting ionic flux through ion channels are among the core and widely used tools for screening drug compounds. Technologies based on these assays are available in fully automated high throughput set-ups and help detect changes in radiolabeled or non-radiolabeled ionic flux. Aurora’s Ion Channel Reader (ICR), which works based on label-free technology of flux assay, offers sensitive, accurate, and reproducible measurements to perform drug ranking matching with patch-clamp (gold standard) data. The non-radiolabeled trace-based flux assay coupled with the ICR detects changes in various ion types, including potassium, calcium, sodium, and chloride channels, by using appropriate tracer ions. This technology is now considered one of the very successful approaches for analyzing ion channel activity in modern drug discovery. It could be a successful approach for studying various ion channels and transporters, including the different members of the TRP family of ion channels.
High-Precision Ion Beam Figuring of X-Ray Plane Mirrors for the Bendable KB Focusing System
Authors: Zhang Yunyang , Huang Qiushi , Yan Shuai , Yu Jun , Huang Handan , He Yumei , Luo Hongxin , Liu Zhi , Zhang Zhong , Wang Zhanshan
Published: May 2022

Two trapezoidal plane mirrors of 240 mm in length were fabricated by ion beam figuring (IBF) technology for application in a bendable KB focusing system. The correction of surface height and slope errors in different spatial frequency ranges of the mirrors was studied systematically. After one to two iterations of IBF, the figure height errors of the vertical focusing mirror (VFM) and horizontal focusing mirror (HFM) were improved from 32.4 and 65.4 nm to 2.7 and 7.2 nm (RMS), respectively. If the best-fit sphere of the surface profile was subtracted, the residual two-dimensional height errors were only 1.1 and 1.2 nm (RMS). The slope errors in the low spatial frequency range were corrected much faster than the middle frequency ones (f = ∼1 mm−1), which make the low-frequency slope error much smaller. After IBF, the two-dimensional slope errors of the two mirrors calculated with a spatial interval of 1 and 10 mm were reduced to approximately 0.29 and 0.08 μrad, respectively. Full spatial frequency characterization of the VFM before and after IBF showed that the low-frequency figure errors (f < 1 mm−1) were significantly reduced while the middle- and high-frequency morphologies (f > 1–2 mm−1) remain almost the same as before figuring. The fabricated plane mirrors were applied in the hard X-ray micro-focusing beamline in the Shanghai Synchrotron Radiation Facility (SSRF), which realized a focal spot of 2.4 μm × 2.8 μm at 10 keV.
Osmoregulation and the Hypothalamic Supraoptic Nucleus: From Genes to Functions
Authors: Mecawi André Souza , Varanda Wamberto Antonio , da Silva Melina Pires
Published: May 2022

Due to the relatively high permeability to water of the plasma membrane, water tends to equilibrate its chemical potential gradient between the intra and extracellular compartments. Because of this, changes in osmolality of the extracellular fluid are accompanied by changes in the cell volume. Therefore, osmoregulatory mechanisms have evolved to keep the tonicity of the extracellular compartment within strict limits. This review focuses on the following aspects of osmoregulation: 1) the general problems in adjusting the “milieu interieur” to challenges imposed by water imbalance, with emphasis on conceptual aspects of osmosis and cell volume regulation; 2) osmosensation and the hypothalamic supraoptic nucleus (SON), starting with analysis of the electrophysiological responses of the magnocellular neurosecretory cells (MNCs) involved in the osmoreception phenomenon; 3) transcriptomic plasticity of SON during sustained hyperosmolality, to pinpoint the genes coding membrane channels and transporters already shown to participate in the osmosensation and new candidates that may have their role further investigated in this process, with emphasis on those expressed in the MNCs, discussing the relationships of hydration state, gene expression, and MNCs electrical activity; and 4) somatodendritic release of neuropeptides in relation to osmoregulation. Finally, we expect that by stressing the relationship between gene expression and the electrical activity of MNCs, studies about the newly discovered plastic-regulated genes that code channels and transporters in the SON may emerge.