bluuebunny/crossref_metadata_2025 huggingface dataset:
Statins change the cytokine profile in Trypanosoma cruzi-infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition
Authors: González-Herrera Fabiola , Clayton Natasha S. , Guzmán-Rivera Daniela , Carrillo Ileana , Castillo Christian , Catalán Mabel , Anfossi Renatto , Quintero-Pertuz Helena , Quilaqueo María Elena , Olea-Azar Claudio , Rivera-Meza Mario , Kemmerling Ulrike , Ridley Anne J. , Vivar Raúl , Maya Juan Diego
Published: January 2023

Introduction

Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1β, IL-6, and TNF-α to control parasitemia. Although this response contains parasite infection, it causes damage to the heart tissue. Thus, the use of immunomodulators is a rational alternative to CCC. Rho-associated kinase (ROCK) 1 and 2 are RhoA-activated serine/threonine kinases that regulate the actomyosin cytoskeleton. Both ROCKs have been implicated in the polarization of macrophages towards an M1 (pro-inflammatory) phenotype. Statins are FDA-approved lipid-lowering drugs that reduce RhoA signaling by inhibiting geranylgeranyl pyrophosphate (GGPP) synthesis. This work aims to identify the effect of statins on U937 macrophage polarization and cardiac tissue inflammation and its relationship with ROCK activity during T. cruzi infection.

Methods

PMA-induced, wild-type, GFP-, CA-ROCK1- and CA-ROCK2-expressing U937 macrophages were incubated with atorvastatin, or the inhibitors Y-27632, JSH-23, TAK-242, or C3 exoenzyme incubated with or without T. cruzi trypomastigotes for 30 min to evaluate the activity of ROCK and the M1 and M2 cytokine expression and secretion profiling. Also, ROCK activity was determined in T. cruzi-infected, BALB/c mice hearts.

Results

In this study, we demonstrate for the first time in macrophages that incubation with T. cruzi leads to ROCK activation via the TLR4 pathway, which triggers NF-κB activation. Inhibition of ROCKs by Y-27632 prevents NF-κB activation and the expression and secretion of M1 markers, as does treatment with atorvastatin. Furthermore, we show that the effect of atorvastatin on the NF-kB pathway and cytokine secretion is mediated by ROCK. Finally, statin treatment decreased ROCK activation and expression, and the pro-inflammatory cytokine production, promoting anti-inflammatory cytokine expression in chronic chagasic mice hearts.

Conclusion

These results suggest that the statin modulation of the inflammatory response due to ROCK inhibition is a potential pharmacological strategy to prevent cardiac inflammation in CCC.
Alterations of the gut virome in patients with systemic lupus erythematosus
Authors: Chen Changming , Yan Qiulong , Yao Xueming , Li Shenghui , Lv Qingbo , Wang Guangyang , Zhong Qin , Tang Fang , Liu Zhengqi , Huang Ying , An Yang , Zhou Jing , Zhang Qiongyu , Zhang Aiqin , Ullah Hayan , Zhang Yue , Liu Can , Zhu Dan , Li Hufan , Sun Wen , Ma Wukai
Published: January 2023

Background

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that has been linked to the dysbiosis of the gut microbiome and virome. However, the potential characterization of the gut virome in SLE patients needs to be explored more extensively.

Methods

Herein, we analyzed the gut viral community of 16 SLE patients and 31 healthy controls using both bulk and virus-like particle (VLP)-based metagenomic sequencing of their fecal samples. A total of 15,999 non-redundant viral operational taxonomic units (vOTUs) were identified from the metagenomic assembled contigs and used for gut virome profiling.

Results

SLE patients exhibited a significant decrease in gut viral diversity in the bulk metagenome dataset, but this change was not significant in the VLP metagenome dataset. Also, considerable alterations of the overall gut virome composition and remarkable changes in the viral family compositions were observed in SLE patients compared with healthy controls, as observed in both two technologies. We identified 408 vOTUs (177 SLE-enriched and 231 control-enriched) with significantly different relative abundances between patients and controls in the bulk virome, and 18 vOTUs (17 SLE-enriched in 1 control-enriched) in the VLP virome. The SLE-enriched vOTUs included numerous Siphoviridae, Microviridae, and crAss-like viruses and were frequently predicted to infect Bacteroides, Parabacteroides, and Ruminococcus_E, while the control-enriched contained numerous members of Siphoviridae and Myoviridae and were predicted to infect Prevotella and Lachnospirales_CAG-274. We explored the correlations between gut viruses and bacteria and found that some Lachnospirales_CAG-274 and Hungatella_A phages may play key roles in the virus-bacterium network. Furthermore, we explored the gut viral signatures for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of above 0.95, suggesting the potential of the gut virome in the prediction of SLE.

Conclusion

Our findings demonstrated the alterations in viral diversity and taxonomic composition of the gut virome of SLE patients. Further research into the etiology of SLE and the gut viral community will open up new avenues for treating and preventing SLE and other autoimmune diseases.
MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats
Authors: Madi Saaussan , Xie Fang , Farhangi Kamyar , Hsu Chih-Yang , Cheng Shih-Hsun , Aweda Tolulope , Radaram Bhasker , Slania Stephanie , Lambert Tammy , Rambo Mary , Skedzielewski Tina , Cole Austin , Sherina Valeriia , McKearnan Shannon , Tran Hoang , Alsaid Hasan , Doan Minh , Stokes Alan H. , O’Hagan Derek T. , Maruggi Giulietta , Bertholet Sylvie , Temmerman Stéphane T. , Johnson Russell , Jucker Beat M.
Published: January 2023

The goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01 adjuvanted protein and lipid nanoparticle (LNP) encapsulated Self-Amplifying mRNA (SAM)). MRI and 18FDG PET imaging were performed temporally at baseline, 4, 24, 48, and 72 hr post Prime and Prime-Boost vaccination in hindlimb with Cytomegalovirus (CMV) gB and pentamer proteins formulated with AS01, LNP encapsulated CMV gB protein-encoding SAM (CMV SAM), AS01 or with LNP carrier controls. Both CMV AS01 and CMV SAM resulted in a rapid MRI and PET signal enhancement in hindlimb muscles and draining popliteal lymph node reflecting innate and possibly adaptive immune response. MRI signal enhancement and total 18FDG uptake observed in the hindlimb was greater in the CMV SAM vs CMV AS01 group (↑2.3 – 4.3-fold in AUC) and the MRI signal enhancement peak and duration were temporally shifted right in the CMV SAM group following both Prime and Prime-Boost administration. While cytokine profiles were similar among groups, there was good temporal correlation only between IL-6, IL-13, and MRI/PET endpoints. Imaging mass cytometry was performed on lymph node sections at 72 hr post Prime and Prime-Boost vaccination to characterize the innate and adaptive immune cell signatures. Cell proximity analysis indicated that each follicular dendritic cell interacted with more follicular B cells in the CMV AS01 than in the CMV SAM group, supporting the stronger humoral immune response observed in the CMV AS01 group. A strong correlation between lymph node MRI T2 value and nearest-neighbor analysis of follicular dendritic cell and follicular B cells was observed (r=0.808, P<0.01). These data suggest that spatiotemporal imaging data together with AI/ML approaches may help establish whether in vivo imaging biomarkers can predict local and systemic immune responses following vaccination.
CK2β-regulated signaling controls B cell differentiation and function
Authors: Quotti Tubi Laura , Mandato Elisa , Canovas Nunes Sara , Arjomand Arash , Zaffino Fortunato , Manni Sabrina , Casellato Alessandro , Macaccaro Paolo , Vitulo Nicola , Zumerle Sara , Filhol Odile , Boldyreff Brigitte , Siebel Christian W. , Viola Antonella , Valle Giorgio , Mainoldi Federica , Casola Stefano , Cancila Valeria , Gulino Alessandro , Tripodo Claudio , Pizzi Marco , Dei Tos Angelo Paolo , Trentin Livio , Semenzato Gianpietro , Piazza Francesco
Published: January 2023

Serine-Threonine kinase CK2 supports malignant B-lymphocyte growth but its role in B-cell development and activation is largely unknown. Here, we describe the first B-cell specific knockout (KO) mouse model of the β regulatory subunit of CK2. CK2βKO mice present an increase in marginal zone (MZ) and a reduction in follicular B cells, suggesting a role for CK2 in the regulation of the B cell receptor (BCR) and NOTCH2 signaling pathways. Biochemical analyses demonstrate an increased activation of the NOTCH2 pathway in CK2βKO animals, which sustains MZ B-cell development. Transcriptomic analyses indicate alterations in biological processes involved in immune response and B-cell activation. Upon sheep red blood cells (SRBC) immunization CK2βKO mice exhibit enlarged germinal centers (GCs) but display a limited capacity to generate class-switched GC B cells and immunoglobulins. In vitro assays highlight that B cells lacking CK2β have an impaired signaling downstream of BCR, Toll-like receptor, CD40, and IL-4R all crucial for B-cell activation and antigen presenting efficiency. Somatic hypermutations analysis upon 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Chicken Gamma Globulin (NP-CGG) evidences a reduced NP-specific W33L mutation frequency in CK2βKO mice suggesting the importance of the β subunit in sustaining antibody affinity maturation. Lastly, since diffuse large B cell lymphoma (DLBCL) cells derive from GC or post-GC B cells and rely on CK2 for their survival, we sought to investigate the consequences of CK2 inhibition on B cell signaling in DLBCL cells. In line with the observations in our murine model, CK2 inactivation leads to signaling defects in pathways that are essential for malignant B-lymphocyte activation.
Theoretical analysis and experimental study on physical explosion of stratospheric airship envelope
Authors: Song Lin , Yang Yanchu , Zheng Zhidong , He Zeqing , Zhang Xiaojun , Gao Heng , Guo Xiqing
Published: January 2023

The shock wave released from physical explosion of a pressurized stratospheric airship can produce serious damage to the environment. Shock wave overpressure can measure the degree of damage that an explosion can cause to such things as buildings and the human body. To obtain the overpressure from an airship envelope explosion, explosion energy must first be conducted. Explosion energy is derived based on Brode’s equation, Brown’s equation, and Crowl’s equation. An equivalent TNT computational model is then applied to calculate the overpressure of the explosion energy. In order to verify the accuracy of the computational model, a ground test must be conducted. The experimental result shows that a computational model based on Crowl’s equation is more accurate than the other two. Finally, the effect of geometric scale ratio, pressure difference, and the gas of the explosion overpressure is discussed. This paper can provide a relatively effective calculation method for shock wave overpressure for an airship envelope explosion.
Nanotechnology and COVID-19: Prevention, diagnosis, vaccine, and treatment strategies
Authors: Ayan Sumeyra , Aranci-Ciftci Kubra , Ciftci Fatih , Ustundag Cem B.
Published: January 2023

In December 2019, Coronavirus pandemic (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses, which affected the whole world, is emerged. The details on the epidemiology, infection source, transmission mode, and prognosis of SARS-CoV-2 gave in this review. Universal infection control standards such as hand hygiene, environmental cleanliness, use of personal protective equipment, and quarantine used to prevent the spread of COVID-19 without vaccine. However, many vaccine candidate studies carried out globally with using traditional and technological approaches. Innovations in technology allow the development of nanotechnological tools and the formation of systems that will inactivate SARS-CoV-2 in patients. It expected to include technologies that combine different disciplines, especially robotic applications, antimicrobial nanotechnology, and tissue engineering for the future treatment of COVID-19. This review-based work discusses the relationship of COVID-19 and nanotechnology based working principles.
Carbon and cellulose based nanofillers reinforcement to strengthen carbon fiber-epoxy composites: Processing, characterizations, and applications
Authors: Biswas Pias Kumar , Omole Oluwaseun , Peterson Garrett , Cumbo Eric , Agarwal Mangilal , Dalir Hamid
Published: January 2023

Graphical Abstract

Applications of carbon fiber-epoxy composite structures.
Effect of 2-D nanomaterials on sensitivity of plasmonic biosensor for efficient urine glucose detection
Authors: Yadav Archana , Kumar Shatrughna , Kumar Anil , Sharan Preeta
Published: January 2023

This paper presents a multi-layered Kretschmann configuration-based Surface Plasmon Resonance (SPR) biosensor for the detection of urine glucose. The modelling, simulation, and analysis have been done by using Silver (Ag) and Gold (Au) layer on the low refractive index prism BK-7 separately, which created two structures: structure-I (BK7/Ag/Bio-sample) and structure-II (BK7/Au/Bio-sample). Urine samples from a non-diabetic person (0–15 mg/dL) and a diabetic person (.625 gm/dL, 1.25 gm/dL, 2.5 gm/dL, 5 gm/dL, and 10 gm/dL) with the corresponding refractive indices of 1.335, 1.336, 1.337, 1.338, 1.341, and 1.347, respectively, have been used as a bio-sample that has been put on the top layer of the sensor. An investigation was conducted to improve the performance parameters of the proposed plasmonic biosensor by layering different 2-D nanomaterials (graphene, BP) and TMDC materials (MoS2, MoSe2, WS2, and WSe2) over the silicon (Si) layer in both structures at a visible wavelength of 633 nm, using Transfer Matrix Method (TMM). With layer thickness optimization, Structure-I (BK7/Ag (56 nm/Si (3 nm)/WS2 (.8 nm)/Bio-sample) shows a sensitivity of 200 °/RIU which is enhanced up to 1.7 times that of the conventional biosensor (BK7/Ag/Bio-sample) and 1.3 times that of the BK7/Ag (56 nm)/Si (3 nm)/Bio-sample based biosensor. Whereas in Structure-II (BK7/Au (50 nm)/Si (3 nm)/BP (.53 nm)/Bio-sample) with optimised layer thickness, we obtained a sensitivity of 273.4°/RIU, which is enhanced up to 2.2 times that of the conventional biosensor (BK7/Au/Bio-sample) and 1.3 times that of the BK7/Au (50 nm)/Si (3 nm)/Bio-sample. Other performance parameters such as detection accuracy for Structure-I and Structure-II are .5617 degree−1 and .134 degree−1 respectively. The Figure of merit for Structure-I and Structure-II are 112.35/RIU and 36.89/RIU respectively. Therefore, we expect Structure-I (BK7/Ag (56 nm/Si (3 nm)/WS2 (.8 nm)/Bio-sample) and Structure-II (BK7/Au (50 nm)/Si (3 nm)/BP (.53 nm)/Bio-sample) have the potential to detect the glucose concentration with quick response and high sensitivity in terms of the resonance angle shift in SPR curves.
The impact of pre-operative axial length on myopic shift 3 years after congenital and developmental cataract surgery and intraocular lens implantation
Authors: Zhou Xiyue , Fan Fan , Liu Xin , Yang Jianing , Yang Tianke , Luo Yi
Published: January 2023

Purpose

To investigate the impact of the pre-operative axial length (AL) on myopic shift (MS) 3 years after primary intraocular lens (IOL) implantation in congenital/developmental cataract patients.

Methods

A retrospective study of patients who underwent congenital/developmental cataract surgery and primary IOL implantation at age 2–3 years at EENT Hospital was conducted. All patients were followed up regularly for at least 3 years after surgery. Refractive outcomes, including spherical equivalent (SE) and MS, were collected at each follow-up.

Results

Forty eyes from 40 patients were included. The mean age at surgery was 2.56 ± 0.57 years old, and the mean follow-up time was 3.05 ± 0.22 years. Patients were divided into two groups: Group 1 included 20 patients with longer pre-operative ALs (≥22 mm), and Group 2 included 20 patients with average pre-operative ALs (<22 mm). By the last follow-up, the MS was 2.13 (0.38, 2.63) D in Group 1 and 3.88 (2.85, 5.72) D in Group 2. The post-operative MS in Group 2 was statistically greater than that in Group 1 at 3 years after surgery (P < 0.001).

Conclusion

In congenital/developmental cataract patients who underwent cataract extraction and primary IOL implantation at age 2–3 years, eyes with longer pre-operative ALs had a slower MS than those with average pre-operative ALs 3 years after surgery. This finding could have implications for the target refraction decision in congenital/developmental cataract surgery.
Case report: Individualized pulsed electromagnetic field therapy in a Long COVID patient using the Adaptive Force as biomarker
Authors: Schaefer Laura V. , Bittmann Frank N.
Published: January 2023

The increasing prevalence of Long COVID is an imminent public health disaster, and established approaches have not provided adequate diagnostics or treatments. Recently, anesthetic blockade of the stellate ganglion was reported to improve Long COVID symptoms in a small case series, purportedly by “rebooting” the autonomic nervous system. Here, we present a novel diagnostic approach based on the Adaptive Force (AF), and report sustained positive outcome for one severely affected Long COVID patient using individualized pulsed electromagnetic field (PEMF) at the area C7/T1. AF reflects the capacity of the neuromuscular system to adapt adequately to external forces in an isometric holding manner. In case, maximal isometric AF (AFisomax) is exceeded, the muscle merges into eccentric muscle action. Thereby, the force usually increases further until maximal AF (AFmax) is reached. In case adaptation is optimal, AFisomaxis ~99–100% of AFmax. This holding capacity (AFisomax) was found to be vulnerable to disruption by unpleasant stimulus and, hence, was regarded as functional parameter. AF was assessed by an objectified manual muscle test using a handheld device. Prior to treatment, AFisomaxwas considerably lower than AFmax for hip flexors (62N= ~28% AFmax) and elbow flexors (71N= ~44% AFmax); i.e., maximal holding capacity was significantly reduced, indicating dysfunctional motor control. We tested PEMF at C7/T1, identified a frequency that improved neuromuscular function, and applied it for ~15 min. Immediately post-treatment, AFisomaxincreased to ~210N(~100% AFmax) at hip and 184N(~100% AFmax) at elbow. Subjective Long COVID symptoms resolved the following day. At 4 weeks post-treatment, maximal holding capacity was still on a similarly high level as for immediately post-treatment (~100% AFmax) and patient was symptom-free. At 6 months the patient's Long COVID symptoms have not returned. This case report suggests (1) AF could be a promising diagnostic for post-infectious illness, (2) AF can be used to test effective treatments for post-infectious illness, and (3) individualized PEMF may resolve post-infectious symptoms.
Portulaca oleracea L. organic acid extract inhibits persistent methicillin-resistant Staphylococcus aureus in vitro and in vivo
Authors: Liu Gengsong , Liu Aijing , Yang Cheng , Zhou Congcong , Zhou Qiaoyan , Li Haizhu , Yang Hongchun , Mo Jiahao , Zhang Zhidan , Li Gonghe , Si Hongbin , Ou Changbo
Published: January 2023

Staphylococcus aureus continues to be one of the most important pathogens capable of causing a wide range of infections in different sites of the body in humans and livestock. With the emergence of methicillin-resistant strains and the introduction of strict laws on antibiotic usage in animals, antibiotic replacement therapy has become increasingly popular. Previous studies have shown that Portulaca oleracea L. extract exerts a certain degree of bacteriostatic effect, although the active ingredients are unknown. In the present study, the antibacterial activity of the organic acid of P. oleracea (OAPO) against S. aureus was examined using a series of experiments, including the minimum inhibitory concentration, growth curve, and bacteriostasis curve. In vitro antibacterial mechanisms were evaluated based on the integrity and permeability of the cell wall and membrane, scanning electron microscopy, and soluble protein content. A mouse skin wound recovery model was used to verify the antibacterial effects of OAPO on S. aureus in vivo. The results showed that OAPO not only improved skin wound recovery but also decreased the bacterial load in skin wounds. Moreover, the number of inflammatory cells and cytokines decreased in the OAPO-treated groups. In summary, this study reports a botanical extract that can inhibit S. aureus in vitro and in vivo, indicating the potential use of OAPO to prevent and control S. aureus infection in the near future.
The ultrasonically treated nanoliposomes containing PCV2 DNA vaccine expressing gC1qR binding site mutant Cap is efficient in mice
Authors: Du Qian , Shi Tengfei , Wang Huaxin , Zhu Changlei , Yang Nan , Tong Dewen , Huang Yong
Published: January 2023

Nowadays, vaccines are broadly used to prevent porcine circovirus type 2 (PCV2) infection-induced expenditures, but the virus is still spreading among pigs. The current PCV2 vaccines all rely on the immunogenicity of Cap, yet our previous studies found that Cap is also the major component mediating the PCV2 infection-induced immune suppression through its interaction with host gC1qR. Thereby, new vaccines are still necessary for PCV2 prevention and control. In this study, we constructed a new PCV2 DNA vaccine expressing the gC1qR binding site mutant Cap. We introduced the Intron A and WPRE elements into the vector to improve the Cap expression level, and fused the IL-2 secretory signal peptides to the N-terminal of Cap to mediate the secretion of Cap. We also screened and selected chemokines CXCL12, CCL22, and CCL25 to migrate dendritic cells. In addition, we contained the vectors with PEI and then ultrasonic them into nano size to enhance the entrance of the vectors. Finally, the animal experiments showed that the new PCV2 DNA vaccine expressing the gC1qR binding site mutant Cap could induce stronger humoral and cellular immune responses than the PCV2 DNA vaccine expressing the wild-type Cap and the non-ultrasonic treated PCV2 DNA vaccine in mice, and protect the mice from PCV2 infection and lung lesions. The results indicate the new PCV2 DNA vaccine expressing the gC1qR binding site mutant Cap has a certain development value, and provide new insight into the development of novel PCV2 vaccines.
Metabolomics of small extracellular vesicles derived from isocitrate dehydrogenase 1-mutant HCT116 cells collected by semi-automated size exclusion chromatography
Authors: Hayasaka Ryosuke , Tabata Sho , Hasebe Masako , Ikeda Satsuki , Hikita Tomoya , Oneyama Chitose , Yoshitake Jun , Onoshima Daisuke , Takahashi Kumiko , Shibata Takahiro , Uchida Koji , Baba Yoshinobu , Soga Tomoyoshi , Tomita Masaru , Hirayama Akiyoshi
Published: January 2023

Cancer-derived small extracellular vesicles (sEVs) are multifunctional particles with a lipid bilayer structure that are involved in cancer progression, such as malignant proliferation, distant metastasis, and cancer immunity evasion. The separation protocol used to isolate sEVs is an important process and thus, several have been developed, including ultracentrifugation (UC), size exclusion chromatography (SEC), and affinity purification using antibodies against sEV surface antigens. However, the effects of different separation methods on sEV components have not been adequately examined. Here, we developed a semi-automated system for collecting sEVs by combining SEC and preparative high-performance liquid chromatography and applied it to metabolome analysis. The developed SEC system could recover sEVs more efficiently and non-destructively than UC, suggesting that it is an appropriate recovery method for metabolic analysis and reflects biological conditions. Furthermore, using the developed SEC system, we performed metabolome analysis of sEVs from isocitrate dehydrogenase 1 (IDH)-mutated human colon HCT116 cells, which produce the oncogenic metabolite, 2-hydroxyglutaric acid (2-HG). IDH1-mutated HCT116 cells released significantly more sEVs than wild-type (WT) cells. The metabolomic profiles of IDH1 mutant and WT cells showed distinct differences between the cells and their sEVs. Notably, in IDH mutant cells, large amounts of 2-HG were detected not only in cells, but also in sEVs. These results indicate that the SEC system we developed has wide potential applications in sEVs research.
Identification and evaluation of midbrain specific longevity-related genes in exceptionally long-lived but healthy mice
Authors: Kim Hyojung , Huh Yu-Jin , Kim Ji Hun , Jo Minkyung , Shin Joo-Heon , Park Sang Chul , Ahn Jee-Yin , Lee Yun-Il , Lee Yunjong
Published: January 2023

Brain aging is a complex biological process that is affected by both genetic background and environment. The transcriptomic analysis of aged human and rodent brains has been applied to identify age-associated molecular and cellular processes for which intervention could possibly restore declining brain functions induced by aging. However, whether these age-associated genetic alterations are indeed involved in the healthy aging of the brain remains unclear. We herein characterized a naturally occurring, extremely long-lived (34 months of age) but healthy mouse group retaining well-preserved motor functions. Strikingly, these long-lived mice maintained tyrosine hydroxylase expression and dopaminergic fiber densities, even in the presence of persistent neuroinflammation and expression of aging markers. Combined with Endeavor gene prioritization, we identified the following midbrain-specific longevity-associated genes in the midbrain of these mice: aimp2, hexb, cacybp, akt2, nrf1, axin1, wwp2, sp2, dnajb9, notch, traf7, and lrp1. A detailed biochemical analysis of the midbrain of these long-lived mice confirmed the increased expression of Nrf1 and the activation of Akt1 and 2. Interestingly, dopaminergic neuroprotective and age-associated E3 ubiquitin ligase parkin expression was retained at high levels in the aforementioned midbrains, possibly supporting the suppression of its toxic substrates AIMP2 and PARIS. In contrast, the 24-month-old mice with dopaminergic neurite deficits failed to maintain parkin expression in the midbrain. AIMP2-induced cytotoxicity, mitochondrial stress, and neurite toxicity can be prevented by overexpression of parkin, Akt1, and Nrf1 in SH-SY5Y and PC12 cells, and basal expression of parkin, Akt1, and Nrf1 is required for maintenance of mitochondrial function and neurite integrity in PC12 cells. Taken together, this longevity-associated pathway could be a potential target of intervention to maintain nigrostriatal dopaminergic fibers and motor ability to ensure healthy longevity.
High clinical diagnostic accuracy of combined salivary gland and myocardial metaiodobenzylguanidine scintigraphy in the diagnosis of Parkinson’s disease
Authors: Li Shuangfang , Yue Lei , Chen Shuzhen , Wu Zhuang , Zhang Jingxing , Hong Ronghua , Xie Ludi , Peng Kangwen , Wang Chenghong , Lin Ao , Jin Lingjing , Guan Qiang
Published: January 2023

Background

Decreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson’s disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well.

Purpose

To evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD).

Methods

Thirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios.

Results

The combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively.

Conclusion

131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.
Changing subplate circuits: Early activity dependent circuit plasticity
Authors: Mukherjee Didhiti , Kanold Patrick O.
Published: January 2023

Early neural activity in the developing sensory system comprises spontaneous bursts of patterned activity, which is fundamental for sculpting and refinement of immature cortical connections. The crude early connections that are initially refined by spontaneous activity, are further elaborated by sensory-driven activity from the periphery such that orderly and mature connections are established for the proper functioning of the cortices. Subplate neurons (SPNs) are one of the first-born mature neurons that are transiently present during early development, the period of heightened activity-dependent plasticity. SPNs are well integrated within the developing sensory cortices. Their structural and functional properties such as relative mature intrinsic membrane properties, heightened connectivity via chemical and electrical synapses, robust activation by neuromodulatory inputs—place them in an ideal position to serve as crucial elements in monitoring and regulating spontaneous endogenous network activity. Moreover, SPNs are the earliest substrates to receive early sensory-driven activity from the periphery and are involved in its modulation, amplification, and transmission before the maturation of the direct adult-like thalamocortical connectivity. Consequently, SPNs are vulnerable to sensory manipulations in the periphery. A broad range of early sensory deprivations alters SPN circuit organization and functions that might be associated with long term neurodevelopmental and psychiatric disorders. Here we provide a comprehensive overview of SPN function in activity-dependent development during early life and integrate recent findings on the impact of early sensory deprivation on SPNs that could eventually lead to neurodevelopmental disorders.
A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease
Authors: Astner-Rohracher Alexandra , Mauritz Matthias , Leitinger Markus , Rossini Fabio , Kalss Gudrun , Neuray Caroline , Retter Elisabeth , Wortmann Saskia B. , Achleitner Melanie T. , Mayr Johannes A. , Trinka Eugen
Published: January 2023

Objectives

New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy.

Case description

In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable.

Conclusion

This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations.
hPG80 (circulating progastrin) as a blood biomarker for high-grade glial tumors: A pilot study
Authors: Casile Melanie , Passildas Judith , Vire Bérengère , Molnar Ioana , Durando Xavier
Published: January 2023

Background

Currently, the long-term prognosis and survival rate of patients with high-grade glial tumors remains poor and there are no biomarkers. hPG80 (circulating progastrin) secreted into the blood by tumor cells has been widely studied in colorectal cancer. Its involvement in tumorigenesis has been demonstrated in the literature. Moreover, according to a recent study, hPG80 is expressed in the blood of cancer patients at a significantly higher concentration than in the control group composed of healthy blood donors.

Methods

The PROGLIO study is a pilot, single-center, longitudinal study that primarily seeks to evaluate circulating plasma hPG80 concentrations over time in patients with high-grade glial tumors. A fasting blood sample will be taken on the start and end day of radiotherapy and during the adjuvant chemotherapy (every 3 cycles). Follow-up monitoring will be performed for 9 months, with a blood sample taken every 3 months on the day of the follow-up MRI. The study plans to recruit 30 patients and recruitment started in February 2022.

Trial registration

ClinicalTrials.gov, ID NCT05157594; registered on October 27, 2021.
Incidence of intra-procedural complications according to the timing of endovascular treatment in ruptured intracranial aneurysms
Authors: Gaudino Chiara , Navone Stefania Elena , Da Ros Valerio , Guarnaccia Laura , Marfia Giovanni , Pantano Patrizia , Peschillo Simone , Triulzi Fabio Maria , Biraschi Francesco
Published: January 2023

Background

Although endovascular treatment of ruptured intracranial aneurysms is well-established, some critical issues have not yet been clarified, such as the effects of timing on safety and effectiveness of the procedure. The aim of our study was to analyze the incidence of intra-procedural complications according to the timing of treatment, as they can affect morbidity and mortality.

Materials and methods

We retrospectively analyzed all patients who underwent endovascular treatment for ruptured intracranial aneurysms at three high flow center. For all patients, imaging and clinical data, aneurysm's type, mean dimension and different treatment techniques were analyzed. Intra-procedural complications were defined as thrombus formation at the aneurysm's neck, thromboembolic events, and rupture of the aneurysm. Patients were divided into three groups according to time between subarachnoid hemorrhage and treatment (<12 h hyper-early, 12–36 h early, and >36 h delayed).

Results

The final study population included 215 patients. In total, 84 patients (39%) underwent hyper-early, 104 (48%) early, and 27 (13%) delayed endovascular treatment. Overall, 69% of the patients were treated with simple coiling, 23% with balloon-assisted coiling, 1% with stent-assisted coiling, 3% with a flow-diverter stent, 3% with an intrasaccular flow disruptor device, and 0.5% with parent vessel occlusion. Delayed endovascular treatment was associated with an increased risk of total intra-procedural complications compared to both hyper-early (p = 0.009) and early (p = 0.004) treatments with a rate of complications of 56% (vs. 29% in hyper-early and 26% in early treated group—p = 0.011 and p = 0.008). The delayed treatment group showed a higher rate of thrombus formation and thromboembolic events. The increased risk of total intra-procedural complications in delayed treatment was confirmed, also considering only the patients treated with simple coiling and balloon-assisted coiling (p = 0.005 and p = 0.003, respectively, compared to hyper-early and early group) with a rate of complications of 62% (vs. 28% in hyper-early and 26% in early treatments—p = 0.007 and p = 0.003). Also in this subpopulation, delayed treated patients showed a higher incidence of thrombus formation and thromboembolic events.

Conclusions

Endovascular treatment of ruptured intracranial aneurysms more than 36 h after SAH seems to be associated with a higher risk of intra-procedural complications, especially thrombotic and thromboembolic events.
Associations between abnormal spontaneous neural activity and clinical variables, eye movements, and event-related potential indicators in major depressive disorder
Authors: Zhang Qinqin , Li Xiaoling , Yan Haohao , Wang Yun , Ou Yangpan , Yu Yang , Liang Jiaquan , Liao Hairong , Wu Wanting , Mai Xiancong , Xie Guojun , Guo Wenbin
Published: January 2023

Background

This study aimed to investigate the correlations between abnormal spontaneous neural activity measured with fractional amplitude of low-frequency fluctuations (fALFF) and clinical variables, eye movements, and event-related potential indicators in patients with major depressive disorder (MDD).

Methods

We recruited 42 patients with MDD and 42 healthy controls (HCs) and collected their clinical variables, eye movement, event-related potential, and resting-state functional magnetic resonance imaging (rs-fMRI) data. The fALFF, support vector machine (SVM), and correlation analysis were used to analyze the data.

Results

The results of the study showed that the fALFF values of the sensorimotor network, including the right middle temporal gyrus, right cerebellar Crus2, left occipital gyrus, and left middle temporal gyrus, were significantly higher compared to HCs. Correlation analysis showed that the abnormal fALFF value of the right cerebellar Crus2 was inversely correlated with the active coping scores of the Simplified Coping Style Questionnaire in the patients (r = −0.307, p = 0.048). No correlation was observed between abnormal fALFF values and other clinical symptoms, neuropsychological tests, eye movements, and event-related potential-related indicators in patients with MDD. fALFF values in the left middle temporal gyrus could be used to distinguish patients with MDD from HCs with an accuracy of 78.57%.

Conclusions

Patients with MDD exhibited enhanced spontaneous neural activity in the sensorimotor network. No associations were found between abnormal spontaneous neural activity and clinical variables, eye movements, and event-related potential related indicators in MDD.
Which sites better represent the sensory function of hands in convalescent stroke patients? A study based on electrophysiological examination
Authors: Liu Yu , Ma Jiang , Li Hong , Shi Wan-ying , Xiao Zheng-hua , Yang Qian , Zhao Qing-qing , Wang Fang , Tao Xiao-lin , Bai Yun-fei
Published: January 2023

Background

Assessing hand sensation in stroke patients is necessary; however, current clinical assessments are time-consuming and inaccurate.

Objective

This study aimed to explore the nature of light touch sensation and two-point discrimination (2-PD) of different hand sites in convalescent stroke patients based on somatosensory evoked potentials (SEP).

Methods

Light touch sensation and 2-PD of the thumb, the index finger, the little finger, thenar, and hypothenar were measured (n = 112) using sensory measurement tools. Sensory differences among the hand sites were then compared. The correlation analysis between SEP and the hemiplegic hand function was made. Sensory functions were divided into three levels: sensory intactness, sensory impairment, and sensory loss.

Results

Light touch sensations were mainly associated with sensory impairment in the finger and palm region. The 2-PD of the finger region was mainly sensory loss and that of the palm region was mainly sensory impairment. There was no statistical difference in the light touch sensation among the sites of the hand. The correlation coefficients between the 2-PD and SEP N20 amplitudes differed. The correlation coefficients of the thenar and hypothenar were the smallest, and that of the finger was the largest. Light touch sensation and 2-PD in patients with stroke were related to the hemiplegic hand function.

Conclusion

Any site on the hand could be selected as the measurement site for light touch sensation. The little finger and hypothenar may be appropriate sites when screening for 2-PD. To improve the patient’s recovery they could receive more sensory stimulation of the hand.
Clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node metastases after esophagectomy
Authors: Ping Zhang , Chanjun Zhen , Wenwen Bai , Mingyue Chen , Quanbing Su , Yajing Wang , Zhiguo Zhou
Published: January 2023

Purpose

To evaluate the clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node (SCLN) metastases after esophagectomy.

Methods

After initial esophagectomy (R0 resection), clinical outcomes in patients with esophageal squamous cell carcinoma with SCLN metastases during follow-up were retrospectively analyzed.

Results

A total of 114 patients were split into two groups: the salvage radiotherapy (SR) (n=89) and the control (NSR) (without salvage radiotherapy, n=25). The overall survival rates of 1 year, 3 years and 5 years were 81.6%, 31.4% and 8.6%, accordingly. The 1-year and 3-year survival after SCLN metastases (SASM) rates were 40.2% and 14.5%, respectively; the median SASM time was 10 months. In the SR group, the SASM rates of 1-year and 3-year were 48.1% and 18.9%, compared to 12.0% and 0% in the NSR group (p<0.001). Patients in the SR group who received combined radiochemotherapy experienced 1-year and 3-year SASM rates of 62.6% and 33.4%, compared to 41.9% and 16.5% with single radiotherapy (p<0.001). The salvage radiation dose revealed that the 1-year and 3-year SASM rates turned out to be 56.5% and 23.4% in group of ≥60 Gy, and 29.2% and 7.5% in group of <60 Gy (p<0.001). According to multivariate analysis, combined visceral metastases (CVM), combined mediastinal failure (CMF), salvage radiotherapy, salvage radiation dose and salvage treatment method possibly were identified as important prognostic variables. After propensity score matching (PSM), the above results were similar to those before PSM, except for that only salvage radiotherapy is possibly independent prognostic variables for survival after SCLN metastases in multivariate analysis.

Conclusion

It is possible that salvage radiotherapy can increase the survival rate of patients who receive SCLN metastases following esophagectomy.
Early hepatoid adenocarcinoma of the stomach with signet ring cell carcinoma: A case report and clinicopathological features
Authors: Wu Xinglong , Di Lianjun , Li Chengfang , Zhang Suyuan , Tan Na , Huang Jiajia , Tuo Biguang
Published: January 2023

Background

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer with poor prognosis, and its clinicopathological features are not well understood, so the pathology from the clinical biopsy is easily misdiagnosed, especially for special or atypical HAS. We present an extremely rare early HAS with signet ring cell carcinoma and evaluate its clinicopathological features.

Case presentation

A 51-year-old female patient of Chinese Han ethnicity with upper abdominal pain for 5 years and worsened abdominal pain for 1 month was admitted to our hospital. Esophagogastroduodenoscopy showed a submucosal tumor-like elevated lesion with central depression in the greater curvature of the junction between the antrum and body. Histopathological examination from the biopsy revealed medium–low-differentiation adenocarcinoma with signet ring cell carcinoma. Radical gastrectomy was performed, and the final diagnosis was early HAS with signet ring cell carcinoma.

Conclusions

HAS with signet ring cell carcinoma is a special type of HAS and extremely rare. It is first presented for this extremely rare type of HAS, which contributes to strengthen the understanding for the clinicopathological characteristics of HAS and especially promote early detection of HAS.
Research progress on the role and mechanism of miR-671 in bone metabolism and bone-related diseases
Authors: Wang Shaotai , Hu Min , Song Dongsheng , Tang Linjun , Jiang Huan
Published: January 2023

Bone metabolism consists of bone formation and resorption and maintains a dynamic balance in vivo. When bone homeostasis is broken, it can manifest as osteoarthritis (OA), rheumatoid arthritis (RA), osteosarcoma (OS), etc. MiR-671, an important class of non-coding nucleotide sequences in vivo, is regulated by lncRNA and regulates bone metabolism balance by regulating downstream target proteins and activating various signaling pathways. Based on the structure and primary function of miR-671, this paper summarizes the effect and mechanism of miR-671 in bone-related inflammation and cancer diseases, and prospects the application possibility of miR-671, providing reference information for targeted therapy of bone-related disorders.