bluuebunny/crossref_metadata_2025 huggingface dataset:
ProBDNF and its receptors in immune-mediated inflammatory diseases: novel insights into the regulation of metabolism and mitochondria
Authors: Li Qiao , Hu Yue-Zi , Gao Shan , Wang Peng-Fei , Hu Zhao-Lan , Dai Ru-Ping
Published: April 2023

Immune-mediated inflammatory diseases (IMIDs) consist of a common and clinically diverse group of diseases. Despite remarkable progress in the past two decades, no remission is observed in a large number of patients, and no effective treatments have been developed to prevent organ and tissue damage. Brain-derived neurotrophic factor precursor (proBDNF) and receptors, such as p75 neurotrophin receptor (p75NTR) and sortilin, have been proposed to mediate intracellular metabolism and mitochondrial function to regulate the progression of several IMIDs. Here, the regulatory role of proBDNF and its receptors in seven typical IMIDs, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, allergic asthma, type I diabetes, vasculitis, and inflammatory bowel diseases, was investigated.
Haemagglutination inhibition and virus microneutralisation serology assays: use of harmonised protocols and biological standards in seasonal influenza serology testing and their impact on inter-laboratory variation and assay correlation: A FLUCOP collaborative study
Authors: Waldock Joanna , Remarque Edmond J. , Zheng Lingyi , Ho Sammy , Hoschler Katja , Neumann Britta , Sediri-Schön Hanna , Trombetta Claudia M. , Montomoli Emanuele , Marchi Serena , Lapini Giulia , Zhou Fan , Lartey Sarah L. , Cox Rebecca J. , Facchini Marzia , Castrucci Maria Rita , Friel Damien , Ollinger Thierry , Caillet Catherine , Music Nedzad , Palladino Giuseppe , Engelhardt Othmar G. ,   the FLUCOP consortium
Published: April 2023

Introduction

The haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox of standardised serology assays for seasonal influenza. Building upon previous collaborative studies to harmonise the HAI, in this study the FLUCOP consortium carried out a head-to-head comparison of harmonised HAI and MN protocols to better understand the relationship between HAI and MN titres, and the impact of assay harmonisation and standardisation on inter-laboratory variability and agreement between these methods.

Methods

In this paper, we present two large international collaborative studies testing harmonised HAI and MN protocols across 10 participating laboratories. In the first, we expanded on previously published work, carrying out HAI testing using egg and cell isolated and propagated wild-type (WT) viruses in addition to high-growth reassortants typically used influenza vaccines strains using HAI. In the second we tested two MN protocols: an overnight ELISA-based format and a 3-5 day format, using reassortant viruses and a WT H3N2 cell isolated virus. As serum panels tested in both studies included many overlapping samples, we were able to look at the correlation of HAI and MN titres across different methods and for different influenza subtypes.

Results

We showed that the overnight ELISA and 3-5 day MN formats are not comparable, with titre ratios varying across the dynamic range of the assay. However, the ELISA MN and HAI are comparable, and a conversion factor could possibly be calculated. In both studies, the impact of normalising using a study standard was investigated, and we showed that for almost every strain and assay format tested, normalisation significantly reduced inter-laboratory variation, supporting the continued development of antibody standards for seasonal influenza viruses. Normalisation had no impact on the correlation between overnight ELISA and 3-5 day MN formats.
COVID-19 vaccination in patients with primary immunodeficiencies: an international survey on patient vaccine hesitancy and self-reported adverse events
Authors: Pergent Martine , Haerynck Filomeen , Hoste Levi , Gardulf Ann
Published: April 2023

Introduction

The Sars-CoV-2 pandemic caused great concern for this novel virus among patients with primary immunodeficiency (PID) or inborn errors of immunity (IEI) and their families. When COVID-19 vaccination program started, no data existed on adverse events (AEs) in this particular patient population, nor if patients felt hesitancy being vaccinated.

Objectives

To explore i) reasons for COVID-19 vaccination hesitancy, ii) the number and symptoms of AEs and their severity, durability and management.

Method

The organisations International Patient Organisation for Primary Immunodeficiencies (IPOPI), European Society for Immunodeficiencies (ESID) and International Nursing Group for Immunodeficiencies (INGID) distributed a global self-administered online survey.

Results

The survey was completed by 1317 patients (mean 47, range 12-100, years) from 40 countries. 41.7% of the patients denoted some hesitancy to COVID-19 vaccination, mainly having doubts about postvaccination protection related to their underlying PID and concerns about negative long-term effects. More women (22.6%) reported “very” or “pretty much” hesitancy compared to men (16.4%) (P<0.05). The most common systemic AEs were fatigue, muscle/body pain and headache, usually the same day or the day after the vaccination and lasting for 1-2 days. 27.8% of the respondents reported severe systemic AEs after any dose of COVID-19 vaccine. Only a minority (7.8%) of these patients visited a health-care professional and 20 patients (1.5%) were hospitalized or seen at emergency room without specifying subsequent admission at the hospital. Significantly more local and systemic AEs were reported after the second dose. No differences regarding AEs were observed across different PID subgroups or vaccine types.

Conclusion

At the time of the survey, almost half of the patients reported having felt hesitancy to COVID-19 vaccination highlighting the importance and need of developing joint international guidelines and education programs about COVID-19 vaccination. The types of AEs were comparable to healthy controls, but more frequent AEs were reported. Clinical studies and prospective, detailed registration of AEs related to COVID-19 vaccines in this patient population is of great importance. It is crucial to elucidate whether there is a coincidental or causal association between COVID-19 vaccine and some severe systemic AEs. Our data do not contradict that patients with PID can be advised to be vaccinated against COVID-19, in accordance with applicable national guidelines.
Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?
Authors: Giannotta Claudia , Autino Federica , Massaia Massimo
Published: April 2023

In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers. Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers. In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.
The generation, activation, and polarization of monocyte-derived macrophages in human malignancies
Authors: Chaintreuil Paul , Kerreneur Emeline , Bourgoin Maxence , Savy Coline , Favreau Cécile , Robert Guillaume , Jacquel Arnaud , Auberger Patrick
Published: April 2023

Macrophages are immune cells that originate from embryogenesis or from the differentiation of monocytes. They can adopt numerous phenotypes depending on their origin, tissue distribution and in response to different stimuli and tissue environment. Thus, in vivo, macrophages are endowed with a continuum of phenotypes that are rarely strictly pro-inflammatory or anti-inflammatory and exhibit a broad expression profile that sweeps over the whole polarization spectrum. Schematically, three main macrophage subpopulations coexist in human tissues: naïve macrophages also called M0, pro-inflammatory macrophages referred as M1 macrophages, and anti-inflammatory macrophages also known as M2 macrophages. Naïve macrophages display phagocytic functions, recognize pathogenic agents, and rapidly undergo polarization towards pro or anti-inflammatory macrophages to acquire their full panel of functions. Pro-inflammatory macrophages are widely involved in inflammatory response, during which they exert anti-microbial and anti-tumoral functions. By contrast, anti-inflammatory macrophages are implicated in the resolution of inflammation, the phagocytosis of cell debris and tissue reparation following injuries. Macrophages also play important deleterious or beneficial roles in the initiation and progression of different pathophysiological settings including solid and hematopoietic cancers. A better understanding of the molecular mechanisms involved in the generation, activation and polarization of macrophages is a prerequisite for the development of new therapeutic strategies to modulate macrophages functions in pathological situations.
Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss
Authors: Aoki Tsukasa , Hiura Fumitaka , Li Aonan , Yang Nan , Takakura-Hino Nana , Mukai Satoru , Matsuda Miho , Nishimura Fusanori , Jimi Eijiro
Published: April 2023

Periodontal disease is an infectious disease that affects many people worldwide. Disease progression destroys the alveolar bone and causes tooth loss. We have previously shown that alymphoplasia (aly/aly) mice harboring a loss-of-function mutation in the map3k14 gene, which is involved in p100 to p52 processing of the alternative NF-κB pathway, exhibited mild osteopetrosis due to decreased number of osteoclasts, suggesting the alternative NF-κB pathway as a potential drug target for the amelioration of bone disease. In the present study, wild-type (WT) and aly/aly mice were subjected to silk ligation to establish a periodontitis model. Alveolar bone resorption was suppressed in aly/aly mice by decreased numbers of osteoclasts in the alveolar bone in comparison to WT mice. Furthermore, the expression of receptor activator of NF-κB ligand (RANKL) and TNFα (cytokines involved in osteoclast induction in periligative gingival tissue) was decreased. When primary osteoblasts (POBs) and bone marrow cells (BMCs) derived from WT and aly/aly mice were prepared and co-cultured, osteoclasts were induced from WT-derived BMCs, regardless of the origin of the POBs, but hardly formed from aly/aly mouse-derived BMCs. Furthermore, the local administration of an NIK inhibitor, Cpd33, inhibited osteoclast formation and thereby inhibited alveolar bone resorption in the periodontitis model. Therefore, the NIK-mediated NF-κB alternative pathway can be a therapeutic target for periodontal disease.
Non-surgical treatment of hidradenitis suppurativa: the role of cryotherapy
Authors: Dell'Antonia Massimo , Anedda Jasmine , Tatti Alice , Falco Alessandro , Sanna Silvia , Ferreli Caterina , Atzori Laura
Published: April 2023

Background

Hidradenitis suppurativa is a chronic and recurrent inflammatory disease with a great impact on a patient's quality of life, due to the painful involvement of very sensitive areas, such as the groin, mammary area, and genitals, with malodourous discharge. Multiple treatment options are available; however, no single treatment is effective for all patients, and usually, a combination of medical therapy with various surgical and physical procedures is provided. Cryotherapy is not a routine technique to treat HS, although usually available in the majority of medical clinics, and is cheaper than laser and surgical treatments. The aim of this study was to evaluate the effectiveness of cryotherapy on persistent HS nodules, to reduce the burden of local disease.

Materials and methods

Retrospective observational study in all patients treated with liquid nitrogen cryotherapy for persistent nodules of hidradenitis suppurativa in the last 2 years, with at least 6 months of follow-up after the procedure. Disease severity was assessed with Hurley staging and sonographic staging according to SOS-HS (18 MHz probe, Esaote-MyLab™). The results were scored with a 0–3 points scale, as complete remission (3), partial response (2 to 1), or no response (0), after one session of treatment. Local cleansing and antiseptic treatment after the procedure was the same as previously performed in each patient, not to influence recovery.

Results

In total, 23 patients were included, with a total of 71 persistent nodules treated with a single cryotherapy session. The treatment has been effective in 63 out of 71 nodules treated (88.7%), and the patients attested that they recommend the treatment, the discomfort during recovery was minimal, and the management was not different from daily routine. Persistence was considered as having a failure rate (11.3% overall) and occurred in 7.5% of the nodules of the axillary region, 18.2% on the groin, and 11.2% for nodules of the gluteal region.

Conclusion

Cryotherapy is a simple and effective procedure for the treatment of persistent nodules of HS not responding to medical therapy, and it is a valid alternative to local surgery or laser ablation.
A process model representation of the end-of-life phase of a product in a circular economy to identify standards needs
Authors: Mathur Nehika , Last Noah , Morris K. C.
Published: April 2023

The development of secondary sources as industrial feedstocks is important to creating resilient supply chains that contribute towards diverting resources away from landfills, mitigating deleterious environmental impacts, and minimizing market volatility. A major challenge to develop secondary feedstocks is the coordination and digitalization of the large quantities of generated information at each phase of a product’s life cycle. This paper builds upon earlier work that illustrates a top-level model of the activities and information needs to integrate product manufacturing with circular practices. This paper extends the initial work to explore the cyclical nature of Circular Economy (CE) information flows specifically related to product End-of-life. Using the Integrated Definition 0, IDEF0, modeling technique this paper examines the End-of-life function envisioned under a CE manufacturing model [ISO, 2012]. This function is decomposed into subsequent child functions and is analyzed relative to other product life cycle phases. The paper reviews the current global product EoL practices and in the context of the developed IDEF0 model. The proposed framework contributes a detailed description and presentation of information flows and the drivers of change (i.e., feedback loops) that are essential for creating secondary material streams based on the critically analyzing the reviewed literature. The novelty of this study includes the identification of standards and metrics gaps to facilitate quantitative assessment and evaluation in a CE. The study further elucidates the discussion around CE in terms of resource regeneration by ‘designing out waste’ and decoupling economic growth from resource depletion.
Methylprednisolone is related to lower incidence of postoperative bleeding after flow diverter treatment for unruptured intracranial aneurysm
Authors: Dong Linggen , Liu Qingyuan , Chen Xiheng , Zhang Longhui , Wang Jiejun , Peng Qichen , Li Jiangan , He Hongwei , Liu Peng , Lv Ming
Published: April 2023

Background and objectives

Regarding the anti-inflammatory effect, methylprednisolone is a candidate to prevent patients with unruptured intracranial aneurysms (UIAs) from postoperative bleeding (PB) after flow diverter (FD) treatment. This study aimed to investigate whether methylprednisolone is related to a lower incidence of PB after FD treatment for UIAs.

Methods

This study retrospectively reviewed UIA patients receiving FD treatment between October 2015 and July 2021. All patients were observed until 72  h after FD treatment. The patients receiving methylprednisolone (80  mg, bid, for at least 24 h) were considered as standard methylprednisolone treatment (SMT) users, otherwise as non-SMT users. The primary endpoint indicated the occurrence of PB, including subarachnoid hemorrhage, intracerebral hemorrhage, and ventricular bleeding, within 72 h after FD treatment. This study compared the incidence of PB between SMT users and non-SMT users and investigated the protective effect of SMT on PB after FD treatment using the Cox regression model. Finally, after controlling the potential factors related to PB, we performed subgroup analysis to further confirm the protective effect of SMT on PB.

Results

This study finally included 262 UIA patients receiving FD treatment. PB occurred in 11 patients (4.2%), and 116 patients (44.3%) received SMT postoperatively. The median time from the end of surgery to PB was 12.3 h (range: 0.5–48.0 h). SMT users had a lower incidence of PB comparing with non-SMT users (1/116, 0.9% vs. 10/146, 6.8%, respectively; p = 0.017). The multivariate Cox analysis demonstrated that SMT users (HR, 0.12 [95%CI, 0.02–0.94], p = 0.044) had a lower risk of PB postoperatively. After controlling the potential factors related to PB (i.e., gender, irregular shape, surgical methods [FD and FD + coil] and UIA sizes), the patients receiving SMT still had a lower cumulative incidence of PB, comparing with patients receiving non-SMT (all p < 0.05).

Conclusion

SMT was correlated with the lower incidence of PB for patients receiving FD treatment and may be a potential method to prevent PB after the FD treatment.
Clinical features, angio-architectural phenotypes, and treatment strategy of foramen magnum dural arteriovenous fistulas: a retrospective case series study
Authors: Xiao Zhipeng , Gao Weizhen , Zhou Hongyu , Zhang Xiaohua , Dai Jiong , Wan Jieqing , Guo Liemei
Published: April 2023

Background

The rarity and complex angioarchitecture of foramen magnum dural arteriovenous fistulas (DAVFs) make its treatment difficult and controversial. We aimed to describe their clinical features, angio-architectural phenotypes, and treatments, through a case series study.

Methods

We first retrospectively studied cases of foramen magnum DAVFs treated in our Cerebrovascular Center, and then reviewed the published cases on Pubmed. The clinical characteristics, angioarchitecture, and treatments were analyzed.

Results

A total of 55 patients were confirmed with foramen magnum DAVFs, which included 50 men and 5 women, with a mean age of 52.8 years. Most patients presented with subarachnoid hemorrhage (SAH) (21/55) or myelopathy (30/55), depending on the venous drainage pattern. In this group, 21 DAVFs were supplied by only the vertebral artery (VA), three by only the occipital artery (OA), three by only the ascending pharyngeal artery (APA), and the remaining 28 DAVFs were supplied by two or three of these feeding arteries. Most cases (30/55) were treated with only endovascular embolization, 18 cases (18/55) with only surgical disconnection, five cases (5/55) with combined therapy, and two cases rejected treatment. The angiographic outcome of complete obliteration was achieved in most patients (50/55). In addition, two cases of foramen magnum DAVFs were treated by us in a Hybrid Angio-Surgical Suite (HASS) with good outcomes.

Conclusions

Foramen magnum DAVFs are rare and their angio-architectural features are complicated. The treatment option (microsurgical disconnection or endovascular embolization) should be weighed carefully, and combined therapy in HASS could be a more feasible and less invasive treatment option.
Factors associated with knowledge and awareness of stroke in the Iraqi population: a cross-sectional study
Authors: Al-Obaidi Hala , Khidhair Zainab , Jirjees Feras , Barakat Muna , AlSalamat Husam , Kharaba Zelal , Alfoteih Yassen , Haddad Chadia , Mansour Sara , Hallit Souheil , Malaeb Diana , Hosseini Hassan
Published: April 2023

Introduction

Stroke is a highly prevalent condition with high rates of death and disability in Iraq and around the world. Knowledge of stroke and its associated risk factors is essential for disease prevention and rapid response when confronted with a stroke patient.

Purpose

The purpose of this study is to assess stroke knowledge and identify factors associated with awareness among the Iraqi public.

Material and methods

A questionnaire-based, cross-sectional survey was conducted on the Iraqi population. The self-administered online questionnaire contained three sections. The study got ethical approval from the Research Ethics Committee at the University of Baghdad.

Results

The results showed that 26.8% of the participants reported knowledge regarding identifying all risk factors. In addition, 18.4% and 34.8% of the participants recognized all symptoms and mentioned all possible consequences of stroke, respectively. Previous medical history with chronic diseases had essential relationships with the response when faced with a person having an acute stroke. In addition, there was a significant relationship between gender, smoking history, and identification of early stroke symptoms.

Conclusion

There was a lack of knowledge about risk factors for stroke among the participants. There is a need for an awareness program among the Iraqi people to raise their understanding of stroke that can reduce stroke mortality and morbidity.
Intra-arterial tenecteplase is safe and may improve the first-pass recanalization for acute ischemic stroke with large-artery atherosclerosis: the BRETIS-TNK trial
Authors: Zhao Zi-Ai , Qiu Jing , Wang Lu , Zhao Yong-Gang , Sun Xian-Hui , Li Wei , Liu Xin , Li Xiao-Long , Liu Liang , Chen Ming-Rui , Chen Hui-Sheng
Published: April 2023

Background and purpose

The first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.

Materials and methods

The BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4  mg/min) given continuously for 20  min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.

Results

The first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11).

Conclusion

This is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.
Using bioinformatics technology to mine the expression of serum exosomal miRNA in patients with traumatic brain injury
Authors: Huang Xintao , Xu Xinjuan , Wang Ce , Wang Yi , Yang Yajun , Yao Tianle , Bai Rui , Pei Xile , Bai Feirong , Li Panpan
Published: April 2023

Introduction

Traumatic brain injury (TBI) is considered the most common traumatic neurological disease, is associated with high mortality and long-term complications, and is a global public health issue. However, there has been little progress in serum markers for TBI research. Therefore, there is an urgent need for biomarkers that can sufficiently function in TBI diagnosis and evaluation.

Methods

Exosomal microRNA (ExomiR), a stable circulating marker in the serum, has aroused widespread interest among researchers. To explore the level of serum ExomiR after TBI, we quantified ExomiR expression levels in serum exosomes extracted from patients with TBI using next-generation sequencing (NGS) and explored potential biomarkers using bioinformatics screening.

Results

Compared with the control group, there were 245 ExomiR (136 up-regulated and 109 down-regulated) in the serum of the TBI group that changed significantly. We observed serum ExomiRs expression profiles associated with neurovascular remodeling, the integrity of the blood-brain barrier, neuroinflammation, and a cascade of secondary injury, including eight up-regulated ExomiRs (ExomiR-124-3p, ExomiR-137-3p, ExomiR-9-3p, ExomiR-133a-5p, ExomiR-204-3p, ExomiR-519a-5p, ExomiR-4732-5p, and ExomiR-206) and 2 down-regulated ExomiR (ExomiR-21-3p and ExomiR-199a-5).

Discussion

The results revealed that serum ExomiRs might become a new research direction and breakthrough for the diagnosis and pathophysiological treatment of patients with TBI.
Regulation of the E/I-balance by the neural matrisome
Authors: Mueller-Buehl Cornelius , Wegrzyn David , Bauch Juliane , Faissner Andreas
Published: April 2023

In the mammalian cortex a proper excitatory/inhibitory (E/I) balance is fundamental for cognitive functions. Especially γ-aminobutyric acid (GABA)-releasing interneurons regulate the activity of excitatory projection neurons which form the second main class of neurons in the cortex. During development, the maturation of fast-spiking parvalbumin-expressing interneurons goes along with the formation of net-like structures covering their soma and proximal dendrites. These so-called perineuronal nets (PNNs) represent a specialized form of the extracellular matrix (ECM, also designated as matrisome) that stabilize structural synapses but prevent the formation of new connections. Consequently, PNNs are highly involved in the regulation of the synaptic balance. Previous studies revealed that the formation of perineuronal nets is accompanied by an establishment of mature neuronal circuits and by a closure of critical windows of synaptic plasticity. Furthermore, it has been shown that PNNs differentially impinge the integrity of excitatory and inhibitory synapses. In various neurological and neuropsychiatric disorders alterations of PNNs were described and aroused more attention in the last years. The following review gives an update about the role of PNNs for the maturation of parvalbumin-expressing interneurons and summarizes recent findings about the impact of PNNs in different neurological and neuropsychiatric disorders like schizophrenia or epilepsy. A targeted manipulation of PNNs might provide an interesting new possibility to indirectly modulate the synaptic balance and the E/I ratio in pathological conditions.
Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety
Authors: Hao Shun , Shi Wantong , Liu Weiqi , Chen Qi-Yu , Zhuo Min
Published: April 2023

Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient’s overall quality of life. Serotonin (5-HT) in the central nervous system (CNS) has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions–especially anxiety and depression. Its widespread and diverse receptors underlie the functional complexity of 5-HT in the CNS. Recent studies found that both chronic pain and anxiety are associated with synaptic plasticity in the anterior cingulate cortex (ACC), the insular cortex (IC), and the spinal cord. 5-HT exerts multiple modulations of synaptic transmission and plasticity in the ACC and the spinal cord, including activation, inhibition, and biphasic actions. In this review, we will discuss the multiple actions of the 5-HT system in both chronic pain and injury-related anxiety, and the synaptic mechanisms behind them. It is likely that the specific 5-HT receptors would be new promising therapeutic targets for the effective treatment of chronic pain and injury-related anxiety in the future.
Genetic Variations of Vitamin A-Absorption and Storage-Related Genes, and Their Potential Contribution to Vitamin A Deficiency Risks Among Different Ethnic Groups
Authors: Suzuki Masako , Tomita Meika
Published: April 2023

Vitamin A, an essential fat-soluble micronutrient, plays a critical role in the body, by regulating vision, immune responses, and normal development, for instance. Vitamin A deficiency (VAD) is a major cause of xerophthalmia and increases the risk of death from infectious diseases. It is also emerging that prenatal exposure to VAD is associated with disease risks later in life. The overall prevalence of VAD has significantly declined over recent decades; however, the rate of VAD is still high in many low- and mid-income countries and even in high-income countries among specific ethnic/race groups. While VAD occurs when dietary intake is insufficient to meet demands, establishing a strong association between food insecurity and VAD, and vitamin A supplementation is the primary solution to treat VAD, genetic contributions have also been reported to effect serum vitamin A levels. In this review, we discuss genetic variations associated with vitamin A status and vitamin A bioactivity-associated genes, specifically those linked to uptake of the vitamin in the small intestine and its storage in the liver, as well as their potential contribution to vitamin A deficiency risks among different ethnic groups.
Evaluation and Screening of Hypoglycemic Activity of Total Ginsenosides GBE-5 Fraction From Panax Ginseng Berry Based on UHPLC–MS Metabolomics
Authors: Wang Heyu , Tong Yu , Wang Anqi , Li Ying , Lu Bofan , Li Hui , Jiao Lili , Wu Wei
Published: April 2023

Objective

Ginseng berry (GB) was the mature fruit of medicinal and edible herb, Panax ginseng C.A. Meyer, with significant hypoglycemic effect. Ginsenoside was the main hypoglycemic active component of GB. Evaluating and screening the effective components of GB was of great significance to further develop its hypoglycemic effect.

Methods

The polar fractions of ginseng berry extract (GBE) were separated by a solvent extraction, and identified by ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC–MS). The insulin resistance model of HepG2 cells was established, and the hypoglycemic active fraction in GBE polar fractions were screened in vitro. Rat model of type 2 diabetes mellitus (T2DM) was established to verify the hypoglycemic effect of the GBE active fraction. The metabolomic study based on UHPLC–MS was used to analyze the differential metabolites in the serum of T2DM rats after 30 days of intervention with hypoglycemic active GBE fraction. The kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was used to study the main metabolic pathways involved in the regulation of hypoglycemic active parts of GBE.

Results

It was found that GBE-5 fraction had better hypoglycemic activity than other GBE polar fractions in vitro cell hypoglycemic activity screening experiment. After 30 days of treatment, the fasting blood glucose value of T2DM rats decreased significantly by 34.75%, indicating that it had significant hypoglycemic effect. Eighteen differential metabolites enriched in KEGG metabolic pathway were screened and identified in the rat serum from T2DM vs. GBE-5 group, and the metabolic pathways mainly involved in regulation include arachidonic acid (AA) metabolism, linoleic acid (LA) metabolism, unsaturated fatty acid biosynthesis, and ferroptosis.

Conclusions

The hypoglycemic effect of GBE-5 fraction was better than that of total ginsenoside of GB. The AA metabolism, LA metabolism, unsaturated fatty acid biosynthesis, and ferroptosis were the potential metabolic pathways for GBE-5 fraction to exert hypoglycemic regulation.
Prognostic value of systemic immune inflammation index and geriatric nutrition risk index in early-onset colorectal cancer
Authors: Xiang Shuai , Yang Yu-Xiao , Pan Wen-Jun , Li Ying , Zhang Jun-Hao , Gao Yuan , Liu Shanglong
Published: April 2023

Background

Systemic nutritional and inflammatory markers, which are easy to measure are associated with the progression and prognosis of many cancers. Nevertheless, among the various available indicators, optimal prognostic indicators for patients with early-onset colorectal cancer have not been identified. Therefore, the aim of this study was to identify optimal nutritional and inflammatory markers for early-onset colorectal cancer and examine the relationship between systemic nutritional and inflammatory markers before treatment and survival in patients with early-onset colorectal cancer.

Methods

We retrospectively collected data from 236 eligible patients with early-onset colorectal cancer. Area under the prognostic curve (AUC) and concordance index (C-index) were used to compare seven systemic nutritional and inflammatory markers to identify the optimal inflammatory immune markers. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of indicators in the total study population and different subgroups.

Results

The AUC and C-index showed that the systemic immune inflammation index (SII) and geriatric nutrition risk index (GNRI) had higher prognostic values than other systemic nutritional and inflammatory indicators. Compared with patients in the low SII group, those in the high SII group had lower overall survival (HR, 4.42, 95% CI, 2.36–8.27, p = 0.000). Compared with patients in the high GNRI group, those in the low GNRI group had lower overall survival (HR, 0.33, 95% CI, 0.19–0.56, p = 0.000). SII was negatively associated with GNRI (R = −0.3, p < 0.001), and both were correlated with the tumor stage.

Conclusion

SII and GNRI are suitable nutritional and inflammatory factors for predicting OS in patients with early-onset colorectal cancer; high SII and low GNRI were correlated with worse prognoses. Identifying the high inflammatory state and low nutritional state of patients before surgery and conducting active and timely therapeutic interventions could improve patient prognosis.
Mismatch repair deficiency testing in Lynch syndrome-associated urothelial tumors
Authors: Rasmussen Maria , Sowter Peter , Gallon Richard , Durhuus Jon Ambæk , Hayes Christine , Andersen Ove , Nilbert Mef , Schejbel Lone , Høgdall Estrid , Santibanez-Koref Mauro , Jackson Michael S. , Burn John , Therkildsen Christina
Published: April 2023

Introduction

Lynch syndrome-associated cancer develops due to germline pathogenic variants in one of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 or PMS2. Somatic second hits in tumors cause MMR deficiency, testing for which is used to screen for Lynch syndrome in colorectal cancer and to guide selection for immunotherapy. Both MMR protein immunohistochemistry and microsatellite instability (MSI) analysis can be used. However, concordance between methods can vary for different tumor types. Therefore, we aimed to compare methods of MMR deficiency testing in Lynch syndrome-associated urothelial cancers.

Methods

Ninety-seven urothelial (61 upper tract and 28 bladder) tumors diagnosed from 1980 to 2017 in carriers of Lynch syndrome-associated pathogenic MMR variants and their first-degree relatives (FDR) were analyzed by MMR protein immunohistochemistry, the MSI Analysis System v1.2 (Promega), and an amplicon sequencing-based MSI assay. Two sets of MSI markers were used in sequencing-based MSI analysis: a panel of 24 and 54 markers developed for colorectal cancer and blood MSI analysis, respectively.

Results

Among the 97 urothelial tumors, 86 (88.7%) showed immunohistochemical MMR loss and 68 were successfully analyzed by the Promega MSI assay, of which 48 (70.6%) were MSI-high and 20 (29.4%) were MSI-low/microsatellite stable. Seventy-two samples had sufficient DNA for the sequencing-based MSI assay, of which 55 (76.4%) and 61 (84.7%) scored as MSI-high using the 24-marker and 54-marker panels, respectively. The concordance between the MSI assays and immunohistochemistry was 70.6% (p = 0.003), 87.5% (p = 0.039), and 90.3% (p = 1.00) for the Promega assay, the 24-marker assay, and the 54-marker assay, respectively. Of the 11 tumors with retained MMR protein expression, four were MSI-low/MSI-high or MSI-high by the Promega assay or one of the sequencing-based assays.

Conclusion

Our results show that Lynch syndrome-associated urothelial cancers frequently had loss of MMR protein expression. The Promega MSI assay was significantly less sensitive, but the 54-marker sequencing-based MSI analysis showed no significant difference compared to immunohistochemistry. Data from this study alongside previous studies, suggest that universal MMR deficiency testing of newly diagnosed urothelial cancers, using immunohistochemistry and/or sequencing-based MSI analysis of sensitive markers, offer a potentially useful approach to identification of Lynch syndrome cases.
Executive functioning, behavioural, emotional, and cognitive difficulties in school-aged children prenatally exposed to methadone
Authors: Spowart Katherine M. , Reilly Kasey , Mactier Helen , Hamilton Ruth
Published: April 2023

Aim

The aim of this study was to examine executive function and emotional and behavioural difficulties of children aged between 8 and 10 years who had been prenatally exposed to methadone, compared to non-exposed peers.

Methods

Prospective study: third follow-up of an original cohort of 153 children born to methadone-maintained opioid-dependent mothers 2008–2010: previous investigations were at 1–3 days and at 6–7 months of age. Carers completed the Strength and Difficulties Questionnaire (SDQ) and the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF®2). Results were compared between exposed and non-exposed groups.

Results

Carers of 33 of 144 traceable children completed the measures. SDQ responses showed no group differences on subscales of emotional symptoms, conduct problems, or peer relationship problems. A marginally higher proportion of exposed children had a high or very high hyperactivity subscale score. Exposed children scored significantly higher on BRIEF®2 behavioural, emotional, and cognitive regulation indices, and on the global executive composite. After controlling for potentially confounding higher reported maternal tobacco use in the exposed group via regression modelling, the effect of methadone exposure reduced.

Interpretation

This study supports evidence that methadone exposure in utero is associated with adverse neurodevelopmental outcomes in childhood. Challenges in studying this population include difficulties with long-term follow-up and controlling for potentially confounding factors. Further investigation of the safety of methadone and other opioids in pregnancy must include consideration of maternal tobacco use.
Umbilical cord milking-benefits and risks
Authors: Koo Jenny , Kilicdag Hasan , Katheria Anup
Published: April 2023

The most common methods for providing additional placental blood to a newborn are delayed cord clamping (DCC) and umbilical cord milking (UCM). However, DCC carries the potential risk of hypothermia due to extended exposure to the cold environment in the operating room or delivery room, as well as a delay in performing resuscitation. As an alternative, umbilical cord milking (UCM) and delayed cord clamping with resuscitation (DCC-R) have been studied, as they allow for immediate resuscitation after birth. Given the relative ease of performing UCM compared to DCC-R, UCM is being strongly considered as a practical option in non-vigorous term and near-term neonates, as well as preterm neonates requiring immediate respiratory support. However, the safety profile of UCM, particularly in premature newborns, remains a concern. This review will highlight the currently known benefits and risks of umbilical cord milking and explore ongoing studies.
An Herbal Product Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice via Regulating NF-κB/TNF-α Signaling in Macrophages
Authors: Jing Fei , Chen Xi , Xue Jingbo , Huang Kai , Xing Feng , Hu Xudong , Peng Yuan , Liu Chenghai
Published: April 2023

Background and aim: Pro-inflammatory macrophages aggravated progress of pulmonary fibrosis (PF) both in patients and animal models. Fuzheng Huayu (FZHY) formula, a Chinese herbal product, is effective in treating pulmonary fibrosis in our previous study. But its action mechanism against PF relating to macrophage activation was unclear. This study was designed to evaluate the anti-fibrotic and anti-inflammatory roles of FZHY in pulmonary fibrosis and to elucidate the potential mechanisms.

Methods: Network pharmacology was employed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-pulmonary fibrosis. According to the data of bioinformatics analysis, the key pharmacological target for FZHY against PF was screened. The network pharmacological prediction was validated by a series of experimental assays, including CCK8, western blot and immunofluorescence staining. Then molecular mechanism of FZHY on relating to the predictive target were studied in bleomycin induced pulmonary fibrosis in mice with methylprednisolone as a positive control, and in lipopolysaccharide (LPS) stimulated cultured macrophages in culture, respectively.

Results: The network pharmacology analysis reveal that a total of 12 FZHY–PF crossover proteins were filtered into a protein-protein interaction network complex and designated as the potential targets of FZHY against pulmonary fibrosis, while TNF-α signal pathway ranked at the top. FZHY and methylprednisolone could attenuate the lung fibrosis and decrease pulmonary TNF-α expression in bleomycin induced fibrotic mice, without difference between two treatments. While TNF-α was mainly originated from macrophages identified by double fluorescent staining of TNF-α and F4/80. LPS stimulated cultured macrophage polarization and activation demonstrated by the enhance contents of TNF-α and iNOS but decreased level of Arg-1. FZHY could alleviate the LPS stimulated macrophage polarization and activation demonstrated by decreasing TNF-α and iNOS and increasing Arg-1. In particular, FZHY could significantly reduce the production of p65 and the nuclear translocation of phosphorylated p65.

Conclusion: Fuzheng Huayu formula has a good effect against pulmonary fibrosis induced by bleomycin in mice, whose action mechanism was associated with down-regulation of NF-κB/TNF-α signaling pathway in pro-inflammatory macrophages. These findings provided an important strategy for developing new agents against lung fibrosis and accelerated FZHY product application on patients with lung fibrosis.
Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways
Authors: Wang Juan , Gao Huiying , Xie Yuan , Wang Peng , Li Yu , Zhao Junli , Wang Chunlin , Ma Xin , Wang Yuwen , Mao Qinwen , Xia Haibin
Published: April 2023

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.