bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of TolC on the pathogenicity of porcine extraintestinal pathogenic Escherichia coli
Authors: Hu Jin , Wang Dongfang , Huang Xingfa , Yang Yang , Lian Xin , Wang Wenjun , Xu Xiao , Liu Yulan
Published: August 2022

Extraintestinal pathogenic Escherichia coli (ExPEC) is a well-known critical pathogenic zoonosis that causes extraintestinal infections in humans and animals by affecting their immune organs. Recently, research on the outer membrane protein of E. coli, tolerant colicin (TolC), a virulent protein in the formation of the ExPEC efflux pump, has been an attractive subject. However, the pathogenic mechanisms remain unclear. This study aimed to explore the role of TolC in the pathogenesis of the ExPEC strain PPECC42; a complementation strain (Cm-TolC) and an isogenic mutant (ΔTolC) were constructed. Loss of TolC drastically impaired the virulence of ExPEC in an experimental mouse model. ΔTolC showed a substantial decrease in the porcine aortic vascular endothelial cell (PAVEC) adherence, invasion, and pro-inflammatory response, in contrast to that of the wild type, with a reduced survival ratio in both the bacterial load and whole blood in mice. ΔTolC also showed decreased expression of necroptosis signals such as receptor-interacting protein kinase 1, phosphorylated mixed-lineage kinase domain-like protein, and mitochondrial proteins such as phosphoglycerate mutase family member 5. Our data suggest that TolC is closely associated with ExPEC pathogenesis. These results provide scientific grounds for exploring the potential of TolC as an effective drug target for controlling ExPEC infection, screening new inhibitors, and developing new drugs. This will allow for further prevention and control of ExPEC infection.
Metagenomic shotgun sequencing and metabolomic profiling identify specific human gut microbiota associated with diabetic retinopathy in patients with type 2 diabetes
Authors: Li Lihua , Yang Kaibo , Li Cong , Zhang Han , Yu Honghua , Chen Kang , Yang Xiaohong , Liu Lei
Published: August 2022

Background

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) and is one of the leading causes of blindness among DM patients. However, the molecular mechanism involving DR remains unclear.

Methods

A case–control study with age-, sex-, and duration-matched diabetic patients and controls was conducted, which included 15 type 2 DM (T2DM) patients with DR and 15 T2DM patients without DR. Shotgun sequencing and non-targeted metabolomic profiling analyses of fecal samples were performed, and comprehensive bioinformatics analyses were conducted.

Results

Using metagenomic analyses, we identified 293,460 unique genes in the non-DR group, while that in the DR group was 283,235, and the number of overlapping genes was 1,237,914. Regarding phylum levels, Actinobacteria decreased but Bacteroidetes increased in the DR group when compared with those in the control group. Regarding genus levels, Bifidobacterium and Lactobacillus decreased. Cellular processes, environmental information processes, and metabolism-related pathways were found at higher levels in the gut microbiome of DR patients. Using metabolomic analyses, we found 116 differentially expressed metabolites with a positive ion model and 168 differentially expressed metabolites with a negative ion model between the two groups. Kyoto Encyclopedia of Genes and Genomes annotation revealed six pathways with different levels between DR and diabetic controls, namely, cellular processes, environmental information processing, genetic information processing, human diseases, organismal systems and metabolism. Moreover, lysine biosynthesis and lysine degradation were enriched using a positive model, but histidine metabolism and β-alanine metabolism were enriched using a negative model.

Conclusions

Together, the metagenomic profiles of DR patients indicated different gut microbiota compositions and characteristic fecal metabolic phenotypes in DR patients. Our findings of microbial pathways therefore provided potential etiological and therapeutic targets for DR patients.
Antioxidant effect of grape seed extract corrects experimental autoimmune encephalomyelitis behavioral dysfunctions, demyelination, and glial activation
Authors: Mabrouk Maha , El Ayed Mohamed , Démosthènes Amélie , Aissouni Youssef , Aouani Ezzedine , Daulhac-Terrail Laurence , Mokni Meherzia , Bégou Mélina
Published: August 2022

Background and purpose

Multiple sclerosis (MS), a multifactorial autoimmune disease of the central nervous system (CNS), is characterized by demyelination and chronic inflammation, as well as axonal and neuronal loss. There is no cure for MS, and despite a significant improvement in the therapeutic management of patients during the last 20 years, some symptoms are still resistant to treatment, and the evolution of the disease to progressive form seems still ineluctable. The etiology of MS is complex and still not fully understood. However, inflammation is a major driver of physiopathology and oxidative stress contributes to CNS lesions and promotes existing inflammatory response. Plant polyphenols are endowed with many therapeutic benefits through alleviating oxidative stress and inflammation, thus providing neuroprotection in MS. We presently evaluated the curative effect of grape seed extract (GSE) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.

Experimental approach

Six-week-old C57Bl/6J females were subjected to the EAE paradigm (using myelin oligodendrocyte glycoprotein peptide fragment (35-55), complete Freund’s adjuvant, and pertussis toxin) and then chronically treated with GSE from day 10 to day 30 post-induction. Clinical score and body weight were monitored daily, while evaluation of sensitive, motor, cognitive, and anxiety-related behaviors was performed weekly. Then, the GSE effect was evaluated on whole brain and spinal cord samples through the evaluation of oxidative stress damage, antioxidant capacities, myelin alteration, astroglial and microglial proliferation, and sirtuin expression.

Key results

Grape seed extract curative chronic treatment corrected the clinical course of EAE, as well as the mechanical hypersensitivity, and avoided the development of EAE mouse thermal cold allodynia. The neuropathological evaluation showed that GSE reduced oxidative stress in the brain and spinal cord by decreasing the lipid and protein oxidation through correction of the three main antioxidant enzyme activities, namely, superoxide dismutase, catalase, and glutathione peroxidase, as well as restoring normal myelin protein expression and correcting microglial and astroglial protein overexpression and sirtuin downregulation.

Conclusion and implications

These data strongly support GSE as an effective therapeutic approach in MS treatment.
Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report
Authors: Sun Hongwei , Xing Chongyun , Jiang Songfu , Yu Kang , Dai Shengjie , Kong Hongru , Jin Yuepeng , Shan Yunfeng , Yang Wenjun , Wang Zhen , Xiao Jun , Wang Huamao , Wang Wei , Li Zonghai , Shi Keqing
Published: August 2022

The clinical efficacy of current therapies for Hepatocellular carcinoma (HCC) are unsatisfactory. In recent years, chimeric antigen receptor (CAR) T-cell therapies have been developed for solid tumors including advanced HCC (aHCC), but limited progress has been made. Glypican-3 is a promising immunotherapeutic target for HCC since it is specifically highly expressed in HCC. A previous study indicated that GPC3-targeted CAR T-(CAR-GPC3) cells were well-tolerated and had prolonged survival for HCC patients and that Sorafenib could increase the antitumor activities of CAR-GPC3 T-cells against HCC in mouse models. Here, we report a patient with aHCC who achieved a complete response (CR) and a long survival period after the combination therapy of CAR-GPC3 T-cell plus sorafenib.

A 60-year-old Asian male diagnosed with hepatitis B virus (HBV) related HCC developed liver recurrence and lung metastasis after liver tumor resection and trans-arterial chemoembolization therapy. The patient also previously received microwave ablation therapy for lung metastasis. After the enrollment, the patient underwent leukapheresis for CAR-GPC3 T-cells manufacturing. Seven days after leukapheresis, the patient started to receive 400 mg of Sorafenib twice daily. The patient received 4 cycles of CAR-GPC3 T cells (CT011) treatment and each cycle was divided into two infusions. Prior to each cycle of CT011 treatment, lymphodepletion was performed. The lymphodepletion regimen was cyclophosphamide 500 mg/m2/day for 2 to 3 days, and fludarabine 20-25 mg/m2/day for 3 to 4 days. A total of 4×109 CAR-GPC3 T cells were infused. The CT011 plus Sorafenib combination therapy was well tolerated. All the ≥ grade 3 AEs were hematological toxicities which were deemed an expected event caused by the preconditioning regimen. This patient obtained partial responses from the 3rd month and achieved CR in the 12th month after the first cycle of CT011 infusion according to the RECIST1.1 assessment. The tumor had no progression for more than 36 months and maintained the CR status for more than 24 months after the first infusion.
Improved induced innate immune response after cART initiation in people with HIV
Authors: Hove-Skovsgaard Malene , Møller Dina Leth , Hald Annemette , Gerstoft Jan , Lundgren Jens , Ostrowski Sisse Rye , Nielsen Susanne Dam
Published: August 2022

Introduction

Impairment of the innate immune function may contribute to the increased risk of bacterial and viral infections in people with HIV (PWH). In this study we aimed to investigate the induced innate immune responses in PWH prior to and after initiation of combinational antiretroviral therapy (cART). Furthermore, we aimed to investigate if the induced innate immune responses before initiation of cART were associated with CD4+ T-cell recovery one year after initiating cART.

Material and method

The induced innate immune response was assessed by the TruCulture®whole blood technique in 32 PWH before cART initiation and after 1, 6 and 12 months. To mimic bacterial and viral infections we used a panel of three stimuli (lipopolysaccharide (LPS), resiquimod (R848), and polyinosinic:polycytidylic acid (Poly I:C)) to stimulate the extracellular Toll-like receptor (TLR) 4 and the intracellular TLR7/8 and TLR3, respectively. The following cytokine responses were analyzed by Luminex 200: Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p40, IL17A, Interferon (IFN)-α, and IFN-γ.

Results

At baseline PWH with nadir CD4+ T-cell count <350 cell/µL had lower levels of LPS-, R848-, and Poly I:C-induced IL-6 and IFN-γ, LPS- and R848-induced TNF-α and IL-12, LPS induced IL-1b, and R848-induced IL-10 than PWH with nadir CD4+ T-cell count >350 cells/µL. The majority (>50%) had induced cytokine concentrations below the reference intervals at baseline which was most pronounced for the LPS- and Poly I:C-induced responses. The induced responses in the whole population improved after 12 months of cART, and more PWH had induced cytokine concentrations within the reference intervals after 12 months. However, the majority of PWH still had LPS-induced INF-α, INF-γ and Poly I:C-induced TNF-α and IL-6 below the reference interval. The induced innate immune responses before cART initiation were not associated with the CD4+ T-cell recovery after 12 months of cART.

Conclusion

The innate immune response was impaired in PWH, with a more pronounced impairment in PWH with low nadir CD4+ T-cell count. Initiation of cART improved the innate immune response, but compared to the reference intervals, some impairment remained in PWH without viral replication.
Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19
Authors: Huang Yongbiao , Yuan Ye , Chen Sheng , Xu Duo , Xiao Lingyan , Wang Xi , Qin Wan , Liu Bo
Published: August 2022

Coronavirus disease 2019 (COVID‐19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.
Function conservation and disparities of zebrafish and human LGP2 genes in fish and mammalian cells responsive to poly(I:C)
Authors: Gong Xiu-Ying , Qu Zi-Ling , Li Yi-Lin , Sun Hao-Yu , Zhao Xiang , Dan Cheng , Gui Jian-Fang , Zhang Yi-Bing
Published: August 2022

Retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) are viral RNA sensors that regulate host interferon (IFN)-mediated antiviral signaling. LGP2 (laboratory genetics and physiology 2) lacks the N-terminal caspase activation and recruitment domains (CARDs) responsible for signaling transduction in the other two RLR proteins, RIG-I and melanoma differentiation associated gene-5 (MDA5). How LGP2 regulates IFN signaling is controversial, and inconsistent results have often been obtained in overexpression assays when performed in fish cells and mammalian cells. Here we report that the differential sensitivity of fish cells and mammalian cells to poly(I:C) transfection conceals the function conservation of zebrafish and human LGP2. In fish cells, overexpression of zebrafish or human LGP2 initially activates IFN signaling in a dose-dependent manner, followed by inhibition at a critical threshold of LGP2 expression. A similar trend exists for LGP2-dependent IFN induction in response to stimulation by low and high concentrations of poly(I:C). In contrast, overexpression of zebrafish or human LGP2 alone in mammalian cells does not activate IFN signaling, but co-stimulation with very low or very high concentrations of poly(I:C) shows LGP2-dependent enhancement or inhibition of IFN signaling, respectively. Titration assays show that LGP2 promotes MDA5 signaling in mammalian cells mainly under low concentration of poly(I:C) and inhibits RIG-I/MDA5 signaling mainly under high concentration of poly(I:C). Our results suggest that fish and human LGP2s switch regulatory roles from a positive one to a negative one in increasing concentrations of poly(I:C)-triggered IFN response.
Cells of matter and life – towards understanding the structuring of particles and plankton patchiness in the Arctic fjords
Authors: Trudnowska Emilia , Dragańska-Deja Katarzyna , Sagan Sławomir , Błachowiak-Samołyk Katarzyna
Published: August 2022

As the environmental conditions are typically not homogenous, especially in coastal regions, they must provide a mosaic of distinct habitats that can be occupied by particles and plankton in a characteristic way. Here we analyze and map the spatio-temporal distribution patterns and the internal structure of 94 patches of various size fractions of particles and plankton studied by fine resolution measurements of two compatible laser counters performed in the upper epipelagial of two Arctic fjords over six summer seasons. Detected patches generally occupied only the minor part of the studied upper water column (on average 12%), and frequently occurred as multi-size-fraction forms. The observed concentrations within the patches were mostly 1.6 times higher than the background concentrations (max 4.1). The patches ranged in size horizontally from 1 to 92 km (median length 12 km) and vertically from 5 to 50 m (median 26 m). Because the designated patches varied in terms of their shapes and internal structure, a novel classification approach to of patches is proposed. Accordingly, seven types of patches were distinguished: Belt, Triangle, Diamond, Flare, Fingers, Flag, and Rosette. The particles and plankton exhibited all types of these distribution patterns, regardless of the size fraction and location. The observed steepening size spectra slopes over years implies that proliferating Atlantic water advection, triggering increasing role of the smallest size fractions, played the crucial role on compositional dynamics on temporal scale. The recurring high concentration patches of particles and plankton near glaciers suggest that their melting, together with biological production, were the strongest factors generating patchiness on the local scale. An observed under several occasions depth differentiation among size fractions building together vertically thin multi-size-fraction patches is an interesting feature for further studies. Even if distribution patterns of particles and plankton did not clearly reflect all patterns in the environmental water structuring, they happened to be related to the presence of glacier runoff, eddy, sea mountain and hot spots of chlorophyll fluorescence.
The essential observations for reconstructing full-depth tidal currents
Authors: Wang Yuzhe , Zhang Yibo , Wang Jianfeng , Lv Xianqing
Published: August 2022

Based on the modal decomposition and least square method, full-depth tidal currents and corresponding internal tidal modes can be obtained from limited observations. Through a series of experiments based on direct observations at the mooring MP1 and synthetic observations at the moorings MP2 and MP3 in the South China Sea, the essential observations for reconstructing full-depth tidal currents are determined. Both observations in the upper ocean (especially near the thermocline) and deep layer (below 500 m) are essential in the reconstruction. For the upper ocean, an up-looking acoustic Doppler current profiler near the thermocline is generally essential, which can also be replaced by at least 2-4 current meters (CMs). The number of CM depends on the complexity and range of buoyancy frequency variation. For the deep layer, more observations are needed as water depth increases. The observations with the CM interval/water depth ratios about 0.2 can effectively reconstruct full-depth tidal currents below 500 m based on one barotropic mode and first three baroclinic modes. Significantly, the CMs in the middle of the deep layer are more important than those at two ends of the deep layer, which may provide more cost-effective design at a small loss of accuracy. Furthermore, the CMs with the depth interval/water depth ratios less than 1/8 in the deep layer can effectively reconstruct full-depth tidal currents with high-mode baroclinic motions.
Calculation of thermodynamic properties and transport parameters of C6F12O
Authors: Li Dajian , Rao Xiajin , Zhang Xiaoxing , Peng Boya , Pan Shaoming , Huang Wei , Ma Shouxiao
Published: August 2022

C6F12O has good insulating properties and has the potential to be used as an insulating medium in gas-insulated equipment. Previous researches show that thermodynamic properties and transport parameters can reflect the microscopic properties of plasma and evaluate the physical properties of gas during gas discharge. In this paper, the thermodynamic and transport properties of C6F12O are calculated based on LTE conditions. According to the type of particles participating in the reaction and the thermal parameters, the number density of particles, the thermodynamic properties and transport parameters in the range of 300–30000 K are calculated. The results show that the conductivity of C6F12O is higher than that of CO2 and N2 at lower temperatures, which is consistent with the properties of most electronegative gases. The thermal conductivity of C6F12O has distinct peaks at 3500, 5500 and 16000 K, respectively. The calculation results can provide a data basis for the subsequent calculation of breakdown and interruption characteristics, which is significant to the design and development of gas insulating equipment.
Electroacupuncture for the treatment of frozen shoulder: A systematic review and meta-analysis
Authors: Heo Jeong-Weon , Jo Jeong-Hun , Lee Jung-Ju , Kang Hee , Choi Tae-Young , Lee Myeong Soo , Kim Jong-In
Published: August 2022

Background

Electroacupuncture (EA) has reportedly been successful in controlling pain, but there have been no systematic reviews examining the impact of EA on patients with frozen shoulder (FS). The purpose of this review is to provide evidence on the safety and efficacy of EA for pain management in patients with FS.

Methods

We searched 11 databases from their inception: EMBASE, the Cochrane Library, PubMed, AMED, one Chinese medical database, and six Korean medical databases. Two researchers independently performed the study selection, data extraction, and assessment. Bias-related risk was evaluated using the Cochrane risk-of-bias assessment tool.

Results

This review included thirteen studies involving 936 patients. The EA group exhibited improvements in FS pain (MD −1.11, 95% CI −1.61 to −0.61, p < 0.0001, I2 = 97%), function (SMD 2.02, 95% CI 0.36–3.69, p < 0.00001, I2 = 97%), and response rates (RR 1.16, 95% CI 1.07–1.25; p = 0.0002; I2 = 0%) over the manual acupuncture (MA) group. As an adjunct treatment, EA improved FS pain (SMD −1.12, 95% CI −1.52 to −0.71, P < 0.00001, I2 = 0) compared to the control treatments. No adverse effects were reported.

Conclusion

EA is reported to improve FS pain and function compared with control treatments. Additionally, EA can be used as an adjunct therapy for FS pain. EA could emerge as a potent intervention against FS.

Systematic review registration

[http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021247090], identifier [CRD42021247090]
Case report: Directional infusion of peripheral blood stem cells into the necrotic zone in femoral heads through the medial circumflex femoral artery: A tracing study
Authors: Mao Qiang , Shao Weijie , Lv Shuaijie , Tong Peijian , He Bangjian
Published: August 2022

Objective

This study aimed to explore whether peripheral blood stem cells (PBSCs) infused through the medial circumflex femoral artery to treat osteonecrosis of the femoral head (ONFH) could migrate into the necrotic area of femoral head.

Methods

We collected PBSCs from a patient who had bilateral ONFH by apheresis technique using COBE spectra apheresis system (COBE BCT Inc, Lakewood, CO, USA) after subcutaneous injections of granulocyte-colony stimulating factor (G-CSF) at a dosage of 10 μg/kg for 4 days to mobilize PBSCs. After that, 100 MBq 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) was used to label PBSCs. 18F-FDG labeled PBSCs were infused into the left femoral head via the medial circumflex femoral artery to treat ONFH. Then the patient was underwent three-dimensional positron emission tomography (3D-PET) examination 60 min after cell infusion to monitor the biological distribution of 18F-FDG-labeled PBSCs, and to observe whether the transplanted PBSCs could migrate into the necrotic area of femoral head.

Results

The total number of monouclear cells in the peripheral blood stem cell suspension was 1.95 × 108 which contained 2.20 × 106 CD34+ cells. The activity of 18F-FDG in the labeled cells was 1.8Bq/103 monouclear cells. 3D-PET imaging showed that 18F-FDG radioactivity was detected in the necrotic area of femoral head, acetabulum and femoral bone marrow cavity after transplantation of 18F-FDG-labeled PBSCs via the medial circumflex femoral artery. It is worth noting that although PBSCs labeled with 18F-FDG were widely distributed around the hip, such as femoral bone marrow cavity, femoral head and acetabulum, PBSCs were generally located in the necrotic area of femoral head.

Conclusions

PBSCs could enter into the femoral head and migrate into the necrotic field of femoral head participating in the repair of osteonecrosis after infusion through the medial circumflex femoral artery.
Polymeric biomaterials in the treatment of posterior segment diseases
Authors: Seah Ivan , Ong Charles , Liu Zengping , Su Xinyi
Published: August 2022

Polymeric biomaterials are biological or synthetic substances which can be engineered to interact with biological systems for the diagnosis or treatment of diseases. These biomaterials have immense potential for treating eyes diseases, particularly the retina—a site of many inherited and acquired diseases. Polymeric biomaterials can be engineered to function both as an endotamponade agent and to prevent intraocular scarring in retinal detachment repair surgeries. They can also be designed as a drug delivery platform for treatment of retinal diseases. Finally, they can be used as scaffolds for cellular products and provide non-viral gene delivery solutions to the retina. This perspective article explains the role of polymeric biomaterials in the treatment of retinal conditions by highlighting recent advances being translated to clinical practice. The article will also identify potential hurdles to clinical translation as future research directions in the field.
Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid
Authors: Benning Louise , Morath Christian , Kühn Tessa , Bartenschlager Marie , Kim Heeyoung , Beimler Jörg , Buylaert Mirabel , Nusshag Christian , Kälble Florian , Reineke Marvin , Töllner Maximilian , Schaier Matthias , Klein Katrin , Blank Antje , Schnitzler Paul , Zeier Martin , Süsal Caner , Bartenschlager Ralf , Tran Thuong Hien , Speer Claudius
Published: August 2022

Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5–7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.
Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review
Authors: Grignaschi Silvia , Sbalchiero Anna , Spinozzi Giuseppe , Palermo Bianca Lucia , Cantarini Claudia , Nardiello Chantal , Cavagna Lorenzo , Olivieri Carla
Published: August 2022

Background

Systemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal and a crucial role has been suggested for the type III receptor, Endoglin (ENG). The aim of this systematic review is to investigate and combine the current clinical and molecular available data, to suggest novel hints for further studies.

Methods

We followed PRISMA guidelines; the search was performed on three databases (MEDLINE, Web of Science, Embase) in date November 2nd, 2021. Subsequent to the exclusion of duplicates, we applied as inclusion criteria: 1. focus on the relationship between ENG and SSc; 2. English language. As exclusion criteria: 1. ENG exclusively as a cellular biomarker; 2. no focus on ENG-SSc relationship; 3. review articles and 4. abstracts that did not add novel data. Eligibility was assessed independently by each author to reduce biases. We divided records into clinical and molecular works and subgrouped them by their study features and aim.

Results

We selected 25 original papers and 10 conference abstracts. Molecular studies included 6 articles and 4 abstracts, whereas clinical studies included 17 articles and 6 abstracts; 2 articles presented both characteristics. Molecular studies were focussed on ENG expression in different cell types, showing an altered ENG expression in SSc-affected cells. Clinical studies mainly suggested that different disease phenotypes can be related to peculiar disregulations in soluble ENG concentrations.

Discussion

Concerning the possible limits of our search, boolean operators in our strings might have been uneffective. However, the use of different strings in different databases should have reduced this issue at a minimum. Another bias can be represented by the selection step, in which we excluded many articles based on the role of Endoglin as a histological vascular marker rather than a signaling receptor. We tried to reduce this risk by performing the selection independently by each author and discussing disagreements. Our systematic review pointed out that ENG has a pivotal role in activating different TGFβ-stimulated pathways that can be crucial in SSc pathogenesis and progression.
Characteristics of falls occurring during rehabilitation in an acute care hospital in older and non-older patients: A retrospective cohort study
Authors: Kinoshita Tokio , Nishimura Yukihide , Umemoto Yasunori , Kawasaki Shinji , Yasuoka Yoshinori , Minami Kohei , Koike Yumi , Tajima Fumihiro
Published: August 2022

Introduction

Although falls are often reported in hospitals and are common in older individuals, no reports on falls during rehabilitation exist. This study evaluated patients with falls occurring during rehabilitation and identified the characteristics of older and non-older patients.

Materials and methods

Our study retrospectively analyzed reports of falls occurring during rehabilitation at a university hospital from April 1, 2020 to March 31, 2022. The survey items included the number of falls in the hospital as a whole and during rehabilitation, age, gender, modified Rankin Scale (mRS) before admission and at the time of fall, functional independence measure (FIM) at admission, patient communication status at the time of fall, and whether a therapist was near the patient. Patients aged ≥ 65 were considered older; aged ≤ 64, non-older; and those with the same age, gender, and clinical department, randomly selected as non-falling patients.

Results

Thirty-five falls occurred during rehabilitation (14 in the non-older and 21 in the older patients), significantly lower than the 945 for the entire hospital, without any significant difference between non-older and older patients. No significant differences in mRS before admission and FIM at admission were noted for both groups in comparison with the non-falling patient group. Furthermore, gender, mRS, FIM, good communication status, and presence of therapist near the patient were similar between non-older and older patients (non-older 71.4%, older 52.4%). Most falls were minor adverse events that did not require additional treatment.

Conclusion

The rate of falls during rehabilitation was much lower than that during hospitalization, and many falls had minimal impact on the patient. It was also difficult to predict falls in daily life and communication situations, and there was no difference in characteristics between the older and non-older groups. Since more than half of the falls occurred during training with the therapist, it is necessary to reconsider the training content.
Establishment of a human cell line with a surface display system for screening and optimizing Na+-taurocholate cotransporting polypeptide-binding peptides
Authors: Wang Pei-yun , Yang Xue , Guo Lin , Wang Yu-wei , Zhang Wen-lu , Sun Yu-xue , Li Jie , Gan Chun-yang , Long Shao-yuan , Liu Jia-jun , Fan Shu-ying , Huang Ai-long , Hu Jie-Li
Published: August 2022

One of the most desirable targets for HBV medications is the sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for the hepatitis B virus (HBV). N-myristoylated preS1 2–48 (Myrcludex B or Hepcludex), an NTCP-binding peptide from the large surface protein of HBV, has been developed as the first-in-class entry inhibitor. However, its relatively large molecular weight contributes to increased immunogenicity and antibody production. As a result, it is preferable to look for an NTCP-binding peptide with a smaller size. To do this, we developed a human cell surface display strategy and screened peptides based on preS1-21. PreS1-21 (genotype D) was extended by 7 random amino acids and fused with mCherry and FasL transmembrane domain. The pooled constructs were transfected into HEK293 cells by using the transposon/transposase system to create a library displaying various peptides on the cell surface with red fluorescence. On the other hand, we expressed NTCP protein fused with EGFP on HEK293 and used the membrane lysate containing NTCP-GFP as the bait protein to select peptides with increased NTCP affinity. After 7 cycles of selection, the deep sequencing results revealed that some polypeptides were more than 1,000 times enriched. Further screening of the mostly enriched 10 peptides yields the peptide preS1-21-pep3. Replacing the preS1-21 sequence of preS1-21-pep3 with those from different genotypes demonstrated that the consensus sequence of genotype A–F had the best performance. The peptide (Myr-preS1-21-pep3) was synthesized and tested on the HepG2-NTCP cell model. The results showed that Myr-preS1-21-pep3 is approximately 10 times more potent than the initial peptide Myr-preS1-21 in preventing HBV infection. In conclusion, we developed a new strategy for screening peptides binding to membrane proteins and identified a new NTCP-binding peptide with a much smaller size than Hepcludex.
Mass spectrometry-based N-glycosylation analysis in kidney disease
Authors: Ren Weifu , Bian Qi , Cai Yan
Published: August 2022

Kidney disease is a global health concern with an enormous expense. It is estimated that more than 10% of the population worldwide is affected by kidney disease and millions of patients would progress to death prematurely and unnecessarily. Although creatinine detection and renal biopsy are well-established tools for kidney disease diagnosis, they are limited by several inevitable defects. Therefore, diagnostic tools need to be upgraded, especially for the early stage of the disease and possible progression. As one of the most common post-translational modifications of proteins, N-glycosylation plays a vital role in renal structure and function. Deepening research on N-glycosylation in kidney disease provides new insights into the pathophysiology and paves the way for clinical application. In this study, we reviewed recent N-glycosylation studies on several kidney diseases. We also summarized the development of mass spectrometric methods in the field of N-glycoproteomics and N-glycomics.
Post-stroke low-frequency whole-body vibration improves cognition in middle-aged rats of both sexes
Authors: Kerr Nadine , Sanchez Juliana , Moreno William Javier , Furones-Alonso Ofelia E. , Dietrich W. Dalton , Bramlett Helen M. , Raval Ami P.
Published: August 2022

Low-frequency whole-body vibration (WBV; 40 Hz), a low impact form of exercise, intervention for a month following moderate transient middle-cerebral artery occlusion (tMCAO) reduces infarct volume and improves motor function in reproductively senescent, middle-aged female rats. Since post-stroke cognitive decline remains a significant problem, the current study aims to investigate the efficacy of WBV in ameliorating post-tMCAO cognitive deficits and to determine the underlying putative mechanism(s) conferring benefits of WBV in middle-aged rats. Middle-aged rats of both sexes were randomly assigned to tMCAO (90 min) or sham surgery followed by exposure to either WBV (twice a day for 15 min each for 5 days a week over a month) or no WBV treatment groups. Following the last WBV treatment, rats were tested for hippocampus-dependent learning and memory using a water maze followed by harvesting brain and blood samples for histopathological and inflammatory marker analyses, respectively. Results show that post-tMCAO WBV significantly lessens cognitive deficits in rats of both sexes. Post-tMCAO WBV significantly decreased circulating pro-inflammatory cytokines and increased serum levels of irisin, a muscle-derived hormone that may play a role in brain metabolism and inflammation regulation, which suggests putative beneficial mechanisms of WBV.
Profiles of Rho, Opn4, c-Fos, and Birc5 mRNA expression in Wistar rat retinas exposed to white or monochromatic light
Authors: Ziółkowska Natalia , Lewczuk Bogdan
Published: August 2022

Despite concern over potential retinal damage linked to exposure to light-emitting-diode (LED) light (particularly blue light), it remains unknown how exposure to low-intensity monochromatic LED light affects the expression of rhodopsin (Rho, a photopigment that mediates light-induced retinal degeneration), melanopsin (Opn4, a blue-light sensitive photopigment), c-Fos (associated with retinal damage/degeneration), and Birc5 (anti-apoptotic). This study investigated the mRNA expression profiles of these genes under exposure to white and monochromatic light (blue, red, green) in the retinas of albino rats under a cycle of 12 h of light and 12 h of darkness. In each group, 32 Wistar rats were exposed to one type of monochromatic-LED or white-fluorescent light for 7 day (150 lx). Retinal samples were taken for qPCR analysis and light and electron microscopy. Blue and green light exposure markedly decreased expression of Rho and Opn4 mRNA and increased expression of Birc5 and c-Fos mRNA (P < 0.05). In retinas from the blue-light group, loss and vesiculation of photoreceptor outer segments were visible, but not in retinas from the red-light and control group. Measurements of the photoreceptor inner and outer segments length revealed, that this length was significantly decreased in the blue- and green-light exposure groups (P < 0.02), but not in the red-light exposure group. Increased expression of Birc5 and decreased expression of Rho and Opn4 after exposure to blue and green light may be early responses that help to reduce light-induced retinal damage.
Sleep alterations following COVID-19 are associated with both neuroinflammation and psychological disorders, although at different times
Authors: Pellitteri Gaia , Surcinelli Andrea , De Martino Maria , Fabris Martina , Janes Francesco , Bax Francesco , Marini Alessandro , Milanic Romina , Piani Antonella , Isola Miriam , Gigli Gian Luigi , Valente Mariarosaria
Published: August 2022

Introduction

By the end of 2019, severe acute respiratory syndrome coronavirus 2 rapidly spread all over the world impacting mental health and sleep habits. Insomnia, impaired sleep quality, and circadian rhythm alterations were all observed during the pandemic, especially among healthcare workers and in patients with acute and post-acute COVID-19. Sleep disruption may induce a pro-inflammatory state associated with an impairment of immune system function.

Objective

We investigated the relationship between sleep alterations, psychological disorders, and inflammatory blood biomarkers in patients with post-acute COVID-19.

Methods

We enrolled 47 subjects diagnosed with COVID-19 pneumonia at Santa Maria della Misericordia University Hospital (Udine, Italy) between March and May 2020. Selected patients were evaluated at 2 months (T1) and 10 months (T2) after discharge. Each time, we collected clinical interviews, neurological examinations, and self-administered questionnaires to assess sleep and life quality, anxiety, depression, and post-traumatic stress disorder. Blood biomarkers of endothelial activation, neuroinflammation, and inflammatory cytokines were also measured at each follow-up. Collected variables were analyzed using comparisons between groups and linear regression models.

Results

Prevalence of insomnia increased from 10.6% up to 27.3% after COVID-19. Poor sleep quality was found in 41.5% of patients at both study visits. At T1 follow-up, poor sleepers showed higher levels of neurofilament light chain, vascular cell adhesion molecule 1, and interleukin 10; no significant associations were found between sleep quality and psychological disorders. At T2 follow-up, lower sleep quality was associated with higher levels of vascular cell adhesion molecule 1 and interleukin 8, but also with higher scores for anxiety, depression, and post-traumatic stress disorder.

Conclusion

Our results suggest an association of poor sleep quality with both psychological disorders and neuroinflammation, although at different times, in previously hospitalized patients with moderate-to-critical COVID-19.
Concussion vs. resignation by submission: Technical–tactical behavior analysis considering injury in mixed martial arts
Authors: Miarka Bianca , Soto Dany A. Sobarzo , Aedo-Muñoz Esteban A. , Maurício Clóvis A. , Müller Vanessa T. , Bragazzi Nicola L. , Brito Ciro José
Published: August 2022

This research study verified the technical–tactical actions during the mixed martial arts (MMA) fights to generate serious enough injury to stop the MMA round, determining technical-tactical potential risk factors for injury in official MMA combats, according to Concussion or Resignation per Submission. A total of 990 rounds with concussions and 627 resignations per submission were considered with severe injury (i.e., a fight ended by a doctor or referee). All injuries were diagnosed and managed by attending ringside physicians during the MMA fights and rounds and had a continuous technical–tactical behavior analysis, p ≤ 0.05. The leading cause of concussion was due to head trauma (~90%), with higher dependence on head strikes scored actions. Comparisons between Concussion and Resignation per Submission combats demonstrated differences between distance head strikes actions [13(6,25) vs. 9(4,18) frequencies], clinch head strikes actions [1(0;4) vs. 1(0;3) frequencies], ground head strikes actions [1(0;8) vs. 2(0;10) frequencies] and takedowns actions [0(0;1) vs. 1(0;2) frequencies]. This information may provide significant evidence regarding the doctor stoppage in concussion combats and when it could be called by officials supervising MMA.
Neural Plasticity in Spinal and Corticospinal Pathways Induced by Balance Training in Neurologically Intact Adults: A Systematic Review
Authors: Sun Yao , Hurd Caitlin L. , Barnes Michelle M. , Yang Jaynie F.
Published: August 2022

Balance training, defined here as training of postural equilibrium, improves postural control and reduces the rate of falls especially in older adults. This systematic review aimed to determine the neuroplasticity induced by such training in younger (18–30 years old) and older adults (≥65 years old). We focused on spinal and corticospinal pathways, as studied with electrophysiology, in people without neurological or other systemic disorders. We were specifically interested in the change in the excitability of these pathways before and after training. Searches were conducted in four databases: MEDLINE, CINAHL, Scopus, and Embase. A total of 1,172 abstracts were screened, and 14 articles were included. Quality of the studies was evaluated with the Downs and Black checklist. Twelve of the studies measured spinal reflexes, with ten measuring the soleus H-reflex. The H-reflex amplitude was consistently reduced in younger adults after balance training, while mixed results were found in older adults, with many showing an increase in the H-reflex after training. The differences in results between studies of younger vs. older adults may be related to the differences in their H-reflexes at baseline, with older adults showing much smaller H-reflexes than younger adults. Five studies measured corticospinal and intracortical excitability using transcranial magnetic stimulation. Younger adults showed reduced corticospinal excitability and enhanced intracortical inhibition after balance training. Two studies on older adults reported mixed results after training. No conclusions could be drawn for corticospinal and intracortical plasticity given the small number of studies. Overall, balance training induced measurable change in spinal excitability, with different changes seen in younger compared to older adults.
From descriptive connectome to mechanistic connectome: Generative modeling in functional magnetic resonance imaging analysis
Authors: Li Guoshi , Yap Pew-Thian
Published: August 2022

As a newly emerging field, connectomics has greatly advanced our understanding of the wiring diagram and organizational features of the human brain. Generative modeling-based connectome analysis, in particular, plays a vital role in deciphering the neural mechanisms of cognitive functions in health and dysfunction in diseases. Here we review the foundation and development of major generative modeling approaches for functional magnetic resonance imaging (fMRI) and survey their applications to cognitive or clinical neuroscience problems. We argue that conventional structural and functional connectivity (FC) analysis alone is not sufficient to reveal the complex circuit interactions underlying observed neuroimaging data and should be supplemented with generative modeling-based effective connectivity and simulation, a fruitful practice that we term “mechanistic connectome.” The transformation from descriptive connectome to mechanistic connectome will open up promising avenues to gain mechanistic insights into the delicate operating principles of the human brain and their potential impairments in diseases, which facilitates the development of effective personalized treatments to curb neurological and psychiatric disorders.