bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian hormone secretion of enteroendocrine cells: implication on pregnancy status
Authors: Homeida Abdelgadir M. , Homeida Mohamed A. , Al-Suhaimi Ebtesam A.
Published: May 2023

The timing of food intake is a key cue for circadian rhythms in humans and animals. In response to food intake, gut hormones called incretin are produced by intestinal enteroendocrine cells in a circadian rhythm that stimulates insulin secretion and regulates body weight and energy expenditure. Pregnancy is associated with the expansion of β cells, the risk of gestational diabetes mellitus, and excessive weight gain. The timing of food intake is a good way to address metabolic complications during pregnancy. The current review focuses on the circadian rhythms and biological actions of enteroendocrine hormones and their associations with pregnancy status, specifically topics like food intake and gut circadian rhythms, the circadian secretion of enteroendocrine peptides, and the effects of these factors during pregnancy.
Triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride-to-high-density lipoprotein cholesterol ratio are the most predictive markers of the metabolically unhealthy phenotype in overweight/obese adolescent boys
Authors: Furdela Viktoriya , Pavlyshyn Halyna , Shulhai Anna-Mariia , Kozak Kateryna , Furdela Mykhailo
Published: May 2023

Introduction

The prevalence of obesity constantly increases worldwide and definitely increases the risk of premature death in early adulthood. While there is no treatment yet with proven efficacy for the metabolic clamp such as arterial hypertension, dyslipidemia, insulin resistance, diabetes type 2, and fatty liver disease, it is imperative to find a way to decrease cardiometabolic complications. Early prevention strategies beginning in childhood are the most logical step to reduce future cardiovascular morbidity and mortality. Therefore, the aim of the current study is to determine the most sensitive and specific predictive markers of the metabolically unhealthy phenotype with high cardiometabolic risk in overweight/obese adolescent boys.

Methods

This study was carried out at the Ternopil Regional Children's hospital (Western Ukraine) and involved 254 randomly chosen adolescent overweight or obese boys [median age was 16.0 (15.0,16.1) years]. A control group of 30 healthy children with proportional body weight comparable in gender and age to the main group was presented. A list of anthropometrical markers with biochemical values of carbohydrate and lipid metabolism with hepatic enzymes was determined. All overweight/obese boys were divided into three groups: 51.2% of the boys with metabolic syndrome (MetS) based on the IDF criteria; 19.7% of the boys were metabolically healthy obese (MHO) without hypertension, dyslipidemia, and hyperglycemia; and the rest of the boys (29.1%) were classified as metabolically unhealthy obese (MUO) with only one criterion (hypertension, dyslipidemia, or hyperglycemia).

Results

Based on multiple logistic regression analysis that included all anthropometric and biochemical values and calculated indexes in boys from the MHO group and MetS, it was revealed that the maximum likelihood in the prediction of MetS makes the combination of triglyceride glucose index, pediatric nonalcoholic fatty liver disease fibrosis index (PNFI), and triglyceride-to-high-density lipoprotein cholesterol ratio (R2 =0.713, p<0.000). By tracing the receiver operating characteristic curve, the model is confirmed as a good predictor of MetS (AUC=0.898, odds ratio=27.111 percentage correct=86.03%) in overweight and obese boys.

Conclusion

Triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride-to-high-density lipoprotein cholesterol ratio are a valuable combination of predictive markers of the metabolically unhealthy phenotype in Ukrainian overweight/obese boys.
Ulmus davidiana 60% edible ethanolic extract for prevention of pericyte apoptosis in diabetic retinopathy
Authors: Kim Iljin , Seo Jieun , Lee Dong Hyun , Kim Yo-Han , Kim Jun-Hyung , Wie Myung-Bok , Byun Jun-Kyu , Yun Jang-Hyuk
Published: May 2023

Diabetic retinopathy (DR) is a disease that causes visual deficiency owing to vascular leakage or abnormal angiogenesis. Pericyte apoptosis is considered one of the main causes of vascular leakage in diabetic retina, but there are few known therapeutic agents that prevent it. Ulmus davidiana is a safe natural product that has been used in traditional medicine and is attracting attention as a potential treatment for various diseases, but its effect on pericyte loss or vascular leakage in DR is not known at all. In the present study, we investigated on the effects of 60% edible ethanolic extract of U. davidiana (U60E) and catechin 7-O-β-D-apiofuranoside (C7A), a compound of U. davidiana, on pericyte survival and endothelial permeability. U60E and C7A prevented pericyte apoptosis by inhibiting the activation of p38 and JNK induced by increased glucose and tumor necrosis factor alpha (TNF-α) levels in diabetic retina. Moreover, U60E and C7A reduced endothelial permeability by preventing pericyte apoptosis in co-cultures of pericytes and endothelial cells. These results suggest that U60E and C7A could be a potential therapeutic agent for reducing vascular leakage by preventing pericyte apoptosis in DR.
Genome-wide identification and bioinformatics analysis of the WRKY transcription factors and screening of candidate genes for anthocyanin biosynthesis in azalea (Rhododendron simsii)
Authors: Wang Cheng , Ye Dan , Li Yan , Hu Peiling , Xu Run , Wang Xiaojing
Published: May 2023

WRKY transcription factors have been demonstrated to influence the anthocyanin biosynthesis in many plant species. However, there is limited knowledge about the structure and function of WRKY genes in the major ornamental plant azalea (Rhododendron simsii). In this study, we identified 57 RsWRKY genes in the R. simsii genome and classified them into three main groups and several subgroups based on their structural and phylogenetic characteristics. Comparative genomic analysis suggested WRKY gene family has significantly expanded during plant evolution from lower to higher species. Gene duplication analysis indicated that the expansion of the RsWRKY gene family was primarily due to whole-genome duplication (WGD). Additionally, selective pressure analysis (Ka/Ks) suggested that all RsWRKY duplication gene pairs underwent purifying selection. Synteny analysis indicated that 63 and 24 pairs of RsWRKY genes were orthologous to Arabidopsis thaliana and Oryza sativa, respectively. Furthermore, RNA-seq data was used to investigate the expression patterns of RsWRKYs, revealing that 17 and 9 candidate genes may be associated with anthocyanin synthesis at the bud and full bloom stages, respectively. These findings provide valuable insights into the molecular mechanisms underlying anthocyanin biosynthesis in Rhododendron species and lay the foundation for future functional studies of WRKY genes.
Radioimmunotherapy in colorectal cancer treatment: present and future
Authors: Shi Jingyi , Sun Zhuang , Gao Zhaoya , Huang Dandan , Hong Haopeng , Gu Jin
Published: May 2023

Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and rational and effective treatment remains a major challenge. Common treatments include multi-modal combinations of surgery, radiotherapy, and chemotherapy; however, recurrence and metastasis rates remain high. The combination of radiotherapy and immunotherapy (radioimmunotherapy [RIT]) may offer new solutions to this problem, but its prospects remain uncertain. This review aimed to summarize the current applications of radiotherapy and immunotherapy, elaborate on the underlying mechanisms, and systematically review the preliminary results of RIT-related clinical trials for CRC. Studies have identified several key predictors of RIT efficacy. Summarily, rational RIT regimens can improve the outcomes of some patients with CRC, but current study designs have limitations. Further studies on RIT should focus on including larger sample sizes and optimizing the combination therapy regimen based on underlying influencing factors.
Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
Authors: Feo-Lucas Lidia , Godio Cristina , Minguito de la Escalera María , Alvarez-Ladrón Natalia , Villarrubia Laura H. , Vega-Pérez Adrián , González-Cintado Leticia , Domínguez-Andrés Jorge , García-Fojeda Belén , Montero-Fernández Carlos , Casals Cristina , Autilio Chiara , Pérez-Gil Jesús , Crainiciuc Georgiana , Hidalgo Andrés , López-Bravo María , Ardavín Carlos
Published: May 2023

Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in Cx3cr1cre:R26-yfp chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry. Our results demonstrate that HDM-induced airway allergic reactions caused severe alveolar dysfunction, leading to alveolar macrophage death, pneumocyte hypertrophy and surfactant dysfunction. SP-B/C proteins were reduced in allergic lung surfactant, that displayed a reduced efficiency to form surface-active films, increasing the risk of atelectasis. Original alveolar macrophages were replaced by monocyte-derived alveolar macrophages, that persisted at least two months after the resolution of allergy. Monocyte to alveolar macrophage transition occurred through an intermediate stage of pre-alveolar macrophage and was paralleled with translocation into the alveolar space, Siglec-F upregulation, and downregulation of CX3CR1. These data support that the severe respiratory disorders caused by asthmatic reactions not only result from bronchiolar inflammation, but additionally from alveolar dysfunction compromising an efficient gas exchange.
CCDC134 facilitates T cell activation through the regulation of early T cell receptor signaling
Authors: Zhang Tianzhuo , Shi Qianwen , Gu Huining , Yu Biaoyi , Yin Sha , Ge Qing , Mo Xiaoning , Liu Xiaofeng , Huang Jing
Published: May 2023

Modulation of surface T cell antigen receptor (TCR) expression is crucial for proper T cell development and maintenance of mature T cell function at steady state and upon stimulation. We previously determined that CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule that served as a potential member of the γc cytokine family, contributes to antitumor responses by augmenting CD8+ T cell-mediated immunity. Here we show that T cell-specific deletion of Ccdc134 decreased peripheral mature CD4+ and CD8+ T cells, which resulted in impaired T cell homeostasis. Moreover, Ccdc134-deficient T cells exhibited an attenuated response to TCR stimulation in vitro, showing lower activation and proliferative capacity. This was further reflected in vivo, rendering mice refractory to T cell-mediated inflammatory and antitumor responses. More importantly, CCDC134 is associated with TCR signaling components, including CD3ϵ, and attenuated TCR signaling in Ccdc134-deficient T cells via altered CD3ϵ ubiquitination and degradation. Taken together, these findings suggest a role for CCDC134 as a positive regulator of TCR-proximal signaling and provide insight into the cell-intrinsic functional consequences of Ccdc134 deficiency in the attenuation of T cell-mediated inflammatory and antitumor responses.
Comparative genomics of the Leukocyte Receptor Complex in carnivores
Authors: Jelinek April L. , Futas Jan , Burger Pamela A. , Horin Petr
Published: May 2023

Background

The mammalian Leukocyte Receptor Complex (LRC) chromosomal region may contain gene families for the killer cell immunoglobulin-like receptor (KIR) and/or leukocyte immunoglobulin-like receptor (LILR) collections as well as various framing genes. This complex region is well described in humans, mice, and some domestic animals. Although single KIR genes are known in some Carnivora, their complements of LILR genes remain largely unknown due to obstacles in the assembly of regions of high homology in short-read based genomes.

Methods

As part of the analysis of felid immunogenomes, this study focuses on the search for LRC genes in reference genomes and the annotation of LILR genes in Felidae. Chromosome-level genomes based on single-molecule long-read sequencing were preferentially sought and compared to representatives of the Carnivora.

Results

Seven putatively functional LILR genes were found across the Felidae and in the Californian sea lion, four to five genes in Canidae, and four to nine genes in Mustelidae. They form two lineages, as seen in the Bovidae. The ratio of functional genes for activating LILRs to inhibitory LILRs is slightly in favor of inhibitory genes in the Felidae and the Canidae; the reverse is seen in the Californian sea lion. This ratio is even in all of the Mustelidae except the Eurasian otter, which has a predominance of activating LILRs. Various numbers of LILR pseudogenes were identified.

Conclusions

The structure of the LRC is rather conservative in felids and the other Carnivora studied. The LILR sub-region is conserved within the Felidae and has slight differences in the Canidae, but it has taken various evolutionary paths in the Mustelidae. Overall, the process of pseudogenization of LILR genes seems to be more frequent for activating receptors. Phylogenetic analysis found no direct orthologues across the Carnivora which corroborate the rapid evolution of LILRs seen in mammals.
Relative contribution of the presence of an estuarine dam and land reclamation to sediment dynamics of the Nakdong Estuary
Authors: Chang Jongwi , Lee Guan-hong , Harris Courtney K. , Figueroa Steven Miguel , Jung Nathalie W.
Published: May 2023

The Nakdong Estuary of Korea is a dramatic example of an urban estuary that has been heavily developed with the installation of two estuarine dams and approximately 17 km2 of tidal flat reclamation. This study aims to understand the relative contribution of the different physical alterations by implementing four model simulations of the COAWST modeling system: (1) present condition, (2) pre-estuarine dam construction, (3) pre-tidal flat reclamation, (4) both pre-estuarine dam construction and pre-reclamation. In Cases 2 and 4, the model grid was modified to extend the Nakdong estuary upriver about 60 km and remove the estuarine dam. In Cases 3 and 4, the model grid was modified to restore the reclaimed tidal flats. All simulations shared the same initial conditions, boundary conditions, and forcing. Then, the simulation results for current velocity, suspended sediment concentration (SSC), and deposition were used to estimate the relative contribution of each alteration. The results showed that the annual, depth-averaged currents for the pre-estuarine dam (Case 2) were 80% faster than the present condition but were 10% slower for Case 3 (no land reclamation case). Likewise, the depth-averaged SSC was higher by about 25 mg/L in the estuary for Case 2, but it was reduced by about 9 mg/L for Case 3. The increase of velocity and SSC for Case 2 resulted from the removal of the estuarine dam, which changed both the tidal properties (tidal amplitude was reduced by about 40 cm) and estuarine circulation (factor of 5 reductions in the vertical salinity gradient), while the decrease for Case 3 was induced by the reduction in sediment accommodation space (15% of water volume) without a change in the circulation. These results also revealed that the estuarine dam enhanced deposition more than the land reclamation that showed very little change. The changes in current velocity, SSC, and deposition for Case 4 (no dam/reclamation) were very similar to Case 2. Overall, this study suggests that the influence of the estuarine dam was larger than that of the land reclamation in the altered Nakdong Estuary. Moreover, the combination of estuarine alterations acted to enhance the effects. These findings can serve as analogs that can be applied to other estuaries where various human alterations have occurred.
Investigating food web structure and system function of an artificial reef ecosystem based on carbon and nitrogen stable isotope analysis: implications for reef management
Authors: Feng Jie , Zhao Xiaolong , Bi Fan , Zhao Wei , Zhao Liang , Song Hao , Yang Meijie , Hu Zhi , Zhou Cong , Shi Pu , Hu Pengpeng , Ma Peizhen , Sun Pengfei , Jiang Han , Xu Jiangling , Zhang Tao
Published: May 2023

Introduction

Food web is an important basis for identifying trophodynamic processes, and evaluating the structural and functional characteristics of ecosystems. The trophodynamics and system function of artificial reef (AR) ecosystems have rarely been examined.

Methods

Stable isotope analysis was used to investigate the food web structure and functions of an artificial reef (AR) ecosystem in this study.

Results and Discussion

The δ13C and δ15N values of particulate organic matter (POM) in AR showed noticeable seasonal changes, and the δ13C value of POM in autumn was significantly higher than that in other seasons (p<0.05). There were no significant seasonal variations in the δ13C values of solid organic matter (SOM), and no significant difference between SOM and POM was observed except in autumn. Moreover, macroalgae did not significantly affect the δ13C values of SOM. Phytoplankton may be the primary nutrient source in the AR ecosystem. The δ13C values of most crustaceans in the AR were approximately between (-17.03 ± 0.22) ‰ – (-17.74 ± 0.07) ‰, higher than those of most fish, indicating that they may have different basal nutrient sources. The trophic level (TL) of invertebrates was between 2.00 and 3.09, and that of fish was between 2.98 and 3.66. The distribution of δ13C and TLs of crustaceans and fish showed that, except for crustaceans, bivalve shellfish and zooplankton might also be important food sources for fish in the AR ecosystem.

Conclusion

The δ13C and δ15N values of most species in the AR showed good continuity, indicating that they may be mainly produced from the AR ecosystem. Migratory species such as Lateolabrax japonicus and Sepiella maindroni showed higher δ13C values, indicating that they may have migrated from other sea areas. To maintain the stability of the ecosystem structure and function of the AR ecosystem, fishing activities should be carried out following the maximum sustainable yield theory. Future research needs to identify the nutritional relationship between AR and its adjacent sea areas, to depict the food web structure of the AR with higher accuracy.
Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis
Authors: Montezuma Thais , Vernal Sebastian , Andrade Elaine Nascimento , Brandão Jurema Guerrieri , de Oliveira Gustavo Laine Araújo , Gomes Ciro Martins
Published: May 2023

Introduction

The present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy.

Methods

We conducted two systematic reviews (protocols CRD42022308272 and CRD42022308260). We searched the PubMed, EMBASE, Web of Science, Scopus, LILACS, Virtual Health Library and Cochrane Library databases, registers of clinical trial databases and gray literature. We included clinical trials evaluating the addition of clofazimine to PB leprosy treatment and the use of clarithromycin for treating patients with rifampicin-resistant leprosy. Risk of bias (RoB) in randomized clinical trials was assessed by the RoB 2 tool and that in non-randomized clinical trials was assessed by the ROBINS-I tool; and the certainty of the evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A meta-analysis of dichotomous outcomes was performed.

Results

For clofazimine, four studies were included. Cure and relapse rates were not different with the addition of clofazimine to PB leprosy treatment and demonstrated very low certainty of evidence. For clarithromycin, six studies were included. Considerable heterogeneity resulted from the difference between comparators, and studies showed no difference in the assessed outcomes with the addition of clarithromycin to rifampicin-resistant leprosy treatment. Mild adverse events were reported for both drugs but did not significantly impact treatment.

Discussion

The effectiveness of both drugs still needs to be determined. Adding clofazimine to PB leprosy treatment may reduce the repercussions of an incorrect operational classification with no apparent relevant side effects.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308272; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308260, identifier: CRD42022308272; CRD42022308260.
The effects of adding exogenous lignocellulose degrading bacteria during straw incorporation in cold regions on degradation characteristics and soil indigenous bacteria communities
Authors: Wang Yunlong , Zhang Xuelian , Lou Zixi , An Xiaoya , Li Xue , Jiang Xinbo , Wang Weidong , Zhao Hongyan , Fu Minjie , Cui Zongjun
Published: May 2023

Low temperature is one of the bottleneck factors that limits the degradation of straw during rice straw incorporation. Determining strategies to promote the efficient degradation of straw in cold regions has become a highly active research area. This study was to investigate the effect of rice straw incorporation by adding exogenous lignocellulose decomposition microbial consortiums at different soil depths in cold regions. The results showed that the lignocellulose was degraded the most efficiently during straw incorporation, which was in deep soil with the full addition of a high-temperature bacterial system. The composite bacterial systems changed the indigenous soil microbial community structure and diminished the effect of straw incorporation on soil pH, it also significantly increased rice yield and effectively enhanced the functional abundance of soil microorganisms. The predominant bacteria SJA-15, Gemmatimonadaceae, and Bradyrhizobium promoted straw degradation. The concentration of bacterial system and the depth of soil had significantly positive correlations on lignocellulose degradation. These results provide new insights and a theoretical basis for the changes in the soil microbial community and the application of lignocellulose-degrading composite microbial systems with straw incorporation in cold regions.
A novel immunohistochemical protocol for paraffin embedded tissue sections using free-floating techniques
Authors: Muniz Partida Carolina , Walters Eric
Published: May 2023

Immunohistochemistry (IHC) is a well-established and widely used protocol used to visualize tissue architecture, protein expression and localization. Free-floating methods for IHC employ tissue sections that are cut from a cryostat or vibratome. The limitations of these tissue sections are tissue fragility, poor morphology, and the need to use sections of 20–50 μm. In addition, there is a void of information regarding the use of free floating immunohistochemical techniques on paraffin embedded tissue. To address this, we developed a free-float IHC protocol with paraffin embedded tissue (PFFP) that saves time, resources, and tissues. PFFP localized GFAP, olfactory marker protein, tyrosine hydroxylase, and Nestin expression in mouse hippocampal, olfactory bulb, striatum, and cortical tissue. Successful localization of these antigens was achieved using PFFP with and without antigen retrieval, with subsequent chromogenic DAB (3,3′-diaminobenzidine) development and immunofluorescence detection methods. The application of the PFFP in combination with methodologies of in situ hybridization, protein/protein interactions, laser capture dissection, and pathological diagnosis expands the versatility of paraffin embedded tissues.
Mnemonic representations in human lateral geniculate nucleus
Authors: Rahmati Masih , Curtis Clayton E. , Sreenivasan Kartik K.
Published: May 2023

There is a growing appreciation for the role of the thalamus in high-level cognition. Motivated by findings that internal cognitive state drives activity in feedback layers of primary visual cortex (V1) that target the lateral geniculate nucleus (LGN), we investigated the role of LGN in working memory (WM). Specifically, we leveraged model-based neuroimaging approaches to test the hypothesis that human LGN encodes information about spatial locations temporarily encoded in WM. First, we localized and derived a detailed topographic organization in LGN that accords well with previous findings in humans and non-human primates. Next, we used models constructed on the spatial preferences of LGN populations in order to reconstruct spatial locations stored in WM as subjects performed modified memory-guided saccade tasks. We found that population LGN activity faithfully encoded the spatial locations held in memory in all subjects. Importantly, our tasks and models allowed us to dissociate the locations of retinal stimulation and the motor metrics of memory-guided saccades from the maintained spatial locations, thus confirming that human LGN represents true WM information. These findings add LGN to the growing list of subcortical regions involved in WM, and suggest a key pathway by which memories may influence incoming processing at the earliest levels of the visual hierarchy.
Complement C4-deficient mice have a high mortality rate during PTZ-induced epileptic seizures, which correlates with cognitive problems and the deficiency in the expression of Egr1 and other immediate early genes
Authors: Veremeyko Tatyana , Jiang Rongcai , He Mingliang , Ponomarev Eugene D.
Published: May 2023

Complement system plays an important role in the immune defense against pathogens; however, recent studies demonstrated an important role of complement subunits C1q, C4, and C3 in normal functions of the central nervous system (CNS) such as non-functional synapse elimination (synapse pruning), and during various neurologic pathologies. Humans have two forms of C4 protein encoded by C4A and C4B genes that share 99.5% homology, while mice have only one C4B gene that is functionally active in the complement cascade. Overexpression of the human C4A gene was shown to contribute to the development of schizophrenia by mediating extensive synapse pruning through the activation C1q-C4-C3 pathway, while C4B deficiency or low levels of C4B expression were shown to relate to the development of schizophrenia and autism spectrum disorders possibly via other mechanisms not related to synapse elimination. To investigate the potential role of C4B in neuronal functions not related to synapse pruning, we compared wildtype (WT) mice with C3- and C4B- deficient animals for their susceptibility to pentylenetetrazole (PTZ)- induced epileptic seizures. We found that C4B (but not C3)–deficient mice were highly susceptible to convulsant and subconvulsant doses of PTZ when compared to WT controls. Further gene expression analysis revealed that in contrast to WT or C3-deficient animals, C4B-deficient mice failed to upregulate expressions of multiple immediate early genes (IEGs) Egrs1-4, c-Fos, c-Jus, FosB, Npas4, and Nur77 during epileptic seizures. Moreover, C4B-deficient mice had low levels of baseline expression of Egr1 on mRNA and protein levels, which was correlated with the cognitive problems of these animals. C4-deficient animals also failed to upregulate several genes downstream of IEGs such as BDNF and pro-inflammatory cytokines IL-1β, IL-6, and TNF. Taken together, our study demonstrates a new role of C4B in the regulation of expression of IEGs and their downstream targets during CNS insults such as epileptic seizures.
Acupuncture for tension-type headache: a systematic review and meta-analysis of randomized controlled trials
Authors: Kang Wen-lin , Xiao Xian-jun , Fan Rong , Zhong Dong-ling , Li Yu-xi , She Jian , Li Juan , Feng Yue , Jin Rong-jiang
Published: May 2023

Background

Tension-type headache (TTH) is the most common neurologic disease worldwide. Acupuncture is commonly applied to treat TTH, but evidence of acupuncture for TTH is contradictory based on previous meta-analyses. Therefore, we conducted this systematic review and meta-analysis to update the evidence of acupuncture for TTH and aimed to provide a valuable reference for clinical application.

Methods

We searched 9 electronic databases from their inceptions to July 1, 2022 for randomized controlled trials (RCTs) of acupuncture for TTH. We also manually searched reference lists and relevant websites, and the experts in this field were consulted for possible eligible studies. Two independent reviewers conducted literature screening, data extraction, and risk of bias assessment. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias of included studies. Subgroup analyses were carried out based on frequency of acupuncture, total sessions, treatment duration, needle retention, types of acupuncture and categories of medication. Data synthesis was performed using Review Manager 5.3 and Stata 16. The Grading of Recommendations Assessment, Development and Evaluation Approach (GRADE) was used to evaluate the certainty of evidence of each outcome. Meanwhile, the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) was used to assess the reporting quality of interventions in clinical trials of acupuncture.

Results

30 RCTs involving 2,742 participants were included. According to ROB 2, 4 studies were considered as low risk, and the rest studies were some concerns. After treatment, compared with sham acupuncture, acupuncture had greater effect in improvement of responder rate [3 RCTs, RR = 1.30, 95%CI (1.13, 1.50), I2 = 2%, moderate certainty] and headache frequency [5 RCTs, SMD = −0.85, 95%CI (−1.58, −0.12), I2 = 94%, very low certainty]. In contrast to medication, acupuncture was more effective to reduce pain intensity [9 RCTs, SMD = −0.62, 95%CI (−0.86, −0.38), I2 = 63%, low certainty]. Adverse events were evaluated in 16 trials, and no serious event associated with acupuncture occurred.

Conclusions

Acupuncture may be an effective and safe treatment for TTH patients. Due to low or very low certainty of evidence and high heterogeneity, more rigorous RCTs are needed to verify the effect and safety of acupuncture in the management of TTH.
Higher levels of narrativity lead to similar patterns of posterior EEG activity across individuals
Authors: Dini Hossein , Simonetti Aline , Bigne Enrique , Bruni Luis Emilio
Published: May 2023

Introduction

The focus of cognitive and psychological approaches to narrative has not so much been on the elucidation of important aspects of narrative, but rather on using narratives as tools for the investigation of higher order cognitive processes elicited by narratives (e.g., understanding, empathy, etc.). In this study, we work toward a scalar model of narrativity, which can provide testable criteria for selecting and classifying communication forms in their level of narrativity. We investigated whether being exposed to videos with different levels of narrativity modulates shared neural responses, measured by inter-subject correlation, and engagement levels.

Methods

Thirty-two participants watched video advertisements with high-level and low-level of narrativity while their neural responses were measured through electroencephalogram. Additionally, participants’ engagement levels were calculated based on the composite of their self-reported attention and immersion scores.

Results

Results demonstrated that both calculated inter-subject correlation and engagement scores for high-level video ads were significantly higher than those for low-level, suggesting that narrativity levels modulate inter-subject correlation and engagement.

Discussion

We believe that these findings are a step toward the elucidation of the viewers’ way of processing and understanding a given communication artifact as a function of the narrative qualities expressed by the level of narrativity.
N6-methyladenosine participates in mouse hippocampus neurodegeneration via PD-1/PD-L1 pathway
Authors: Hu Wen , Xie Hongbo , Zeng Yubing , Pei Pei , Zhan Xiaojun , Wang Shan , Wang Zhenlin
Published: May 2023

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6A shows a definite cell-specific methylation profile and m6A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway.
Postnatal development of the relaxin-3 innervation of the rat medial septum
Authors: Ros-Bernal Francisco , Gil-Miravet Isis , Lucerón Jorge , Navarro-Sánchez Mónica , Castillo-Gómez Esther , Gundlach Andrew L. , Olucha-Bordonau Francisco E.
Published: May 2023

Introduction

The septal area provides a rich innervation to the hippocampus regulating hippocampal excitability to different behavioral states and modulating theta rhythmogenesis. However, little is known about the neurodevelopmental consequences of its alterations during postnatal development. The activity of the septohippocampal system is driven and/or modulated by ascending inputs, including those arising from the nucleus incertus (NI), many of which contain the neuropeptide, relaxin-3 (RLN3).

Methods

We examined at the molecular and cellular level the ontogeny of RLN3 innervation of the septal area in postnatal rat brains.

Results

Up until P13–15 there were only scattered fibers in the septal area, but a dense plexus had appeared by P17 that was extended and consolidated throughout the septal complex by P20. There was a decrease in the level of colocalization of RLN3 and synaptophysin between P15 and P20 that was reversed between P20 and adulthood. Biotinylated 3-kD dextran amine injections into the septum, revealed retrograde labeling present in the brainstem at P10-P13, but a decrease in anterograde fibers in the NI between P10–20. Simultaneously, a differentiation process began during P10–17, resulting in fewer NI neurons double-labeled for serotonin and RLN3.

Discussion

The onset of the RLN3 innervation of the septum complex between P17–20 is correlated with the onset of hippocampal theta rhythm and several learning processes associated with hippocampal function. Together, these data highlight the relevance and need for further analysis of this stage for normal and pathological septohippocampal development.
Effects of aqueous extract from Baiyedancong-Oolong tea on cytochrome P450 enzymes activities, P-gp and OATs transport abilities and transcription levels in mice
Authors: Zhang Miaogao , Qiu Zhenguo
Published: May 2023

Introduction

Recent studies have been conducted on its influence on drug metabolism and its potential mechanisms, among which the most studies have been focused on CYP3A enzymes.

Methods

In this study, Baiyedancong Oolong tea (BOT) was processed by freeze- and hot air-drying techniques separately to obtain the aqueous extracts of freeze-and hot-dried BOT (FBOT and HBOT, respectively). High and low doses of FBOT (1463.7 and 292.74 mg/kg/d, respectively) and HBOT (1454.46 mg/kg/d, 290.89, respectively) were administered to mice for 7 days.

Results

Aqueous extracts from BOT simultaneously improved liver CYP3A, CYP2E1, and CYP2C37 activities and weakened the transport ability of P-gp and OATs in a dose-dependent manner, thus affecting multiple links of oral drug metabolism in liver, intestinal absorption and metabolism, and renal excretion. Moreover, aqueous extracts from BOT significantly increased the mRNA expressions of liver CYP3A11 and CYP2C37 as well as intestinal CYP3A11. Decreased transcription levels of MDR1 encoding P-gp in small intestine and renal OAT1 and OAT3, which was in the same direction as the regulation of the above enzyme activities and transport capacities. Besides, the transcription level of liver CYP2E1 was weakened, which was inconsistent with its corresponding enzyme activity, suggesting that the increased CYP2E1 activity may be caused by other mechanisms.

Conclusion

Daily consumption or high dose administration of BOT and its related products may affect drug absorption, metabolisms, and excretion.
α-Ketoglutarate stimulates cell growth through the improvement of glucose and glutamine metabolism in C2C12 cell culture
Authors: Yang Bingquan , Liu Yuefei , Steinacker Jürgen Michael
Published: May 2023

Introduction

Cellular adaptation to physical training and energy metabolism play an important role during physical exercise. This study sought to investigate the effects of α-KG on cell growth and energy metabolism in C2C12 cell culture.

Methods

C2C12 cells were cultured in media pretreated without (control) or with α-KG at different concentrations, and cells and media were harvested every 24 h for 8 days. From cell counts, specific cell growth rate (SGR) and doubling time were calculated. The content of glucose, glutamine, lactate, and ammonia in media was determined, and the specific consumption rate (SCR) or production rate (SPR) was calculated. Additionally, cell colony-forming efficiency (CFE) was determined.

Results

The control cells showed a CFE at 50%, a typical cell growth curve in the first 5 days with a mean SGR at 0.86/day, and a mean cell count doubling time at 19.4 h. In the group with α-KG at 100 mM, the cells underwent rapid cell death, and thus no further analysis was made. The treatment with α-KG at lower concentrations (0.1 mM and 1.0 mM) led to a higher CFE at 68 and 55%, respectively, whereas those in groups with higher α-KG concentration decreased (10 and 6% for 20 mM and 30 mM α-KG, respectively). The mean SGR was 0.95/day, 0.94/day, 0.77/day, 0.71/day, and 0.65/day for groups treated with α-KG at 0.1, 1.0, 10.0, 20.0, and 30.0 mM, respectively, and the corresponding cell count doubling time was 17.6, 17.8, 20.9, 24.6, and 24.7 h, respectively. In comparison with that of the control group, the mean glucose SCR decreased in all the groups treated with α-KG, while the mean glutamine SCR remained unchanged; the mean lactate SPR increased in the groups treated with α-KG ≥ 20.0 mM. Finally, the mean SPR of ammonia was lower in all α-KG groups than that in the control.

Discussion and conclusion

The treatment with α-KG at lower concentrations increased cell growth whereas at higher concentrations decreased cell growth, and α-KG reduced glucose consumption and ammonia production. Therefore, α-KG stimulates cell growth in a dose-dependent manner, which is likely through the improvement of glucose and glutamine metabolism in a C2C12 culture setting.
Complete remission in a patient with metastatic gastric cancer receiving tislelizumab combined with chemotherapy: a case report
Authors: Zhu Zhe , Dai Pei-Lin , Han Shuai , Qiu Enming , Wang Yu , Li Zhou
Published: May 2023

The prognosis for patients with advanced gastric cancer (AGC) is poor, with limited treatment options available due to the difficulty of resection. In recent years, chemotherapy and immunotherapy for AGC have shown promising efficacy. However, there is a controversy regarding the surgery of primary tumors and/or metastases in patients with stage IV gastric cancer after systematic therapy. Here, we present a 63-year-old retired female of AGC with supraclavicular metastasis with positive PD-L1 and tumor mutational burden-high (TMB-H). After receiving 8 cycles of capecitabine and oxaliplatin (XELOX) in combination with tislelizumab, the patient achieved complete remission (CR). No evidence of recurrence was identified during follow-up. To the best of our knowledge, this is the first case of AGC with supraclavicular metastasis who achieved CR after treatment with tislelizumab. The mechanism of CR was discussed by genomic and recent clinical studies. The results indicated that programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5 may serve as a clinical indication and standard for chemo-immune combination therapy. In combination with other similar reports, patients with microsatellite instability-high/defective mismatch repair (MSI-H/dMMR), (TMB-H), and positive PD-L1 had better sensitivity to tislelizumab. The patient recovered successfully except for symptoms of gastrointestinal hemorrhage during treatment, which may be associated with the treatment cycle and age. Immunotherapy with tislelizumab has been well-established in the treatment of malignant melanoma, lung cancer, and clear-cell kidney cancer, but its efficacy and safety for esophageal and gastric cancers remain to be validated. The CR of our patient suggested the prospects of tislelizumab in the immunotherapy of gastric cancer. Additionally, a watch-and-wait (WW) method maybe offered for patients with AGC who achieved complete clinical remission (CCR) after immune combination therapy if the patient was older or in poor physical condition.
The Chinese herbal medicine Dai-Zong-Fang promotes browning of white adipocytes in vivo and in vitro by activating PKA pathway to ameliorate obesity
Authors: Xu Jing , Zhang Li-Wei , Feng Hui , Tang Yang , Fu Shou-Qiang , Liu Xi-Ming , Zhu Xiao-Yun
Published: May 2023

Introduction: The global prevalence of obesity is rising rapidly. Conversion of white adipose tissue (WAT) into beige adipose tissue with heat-consuming characteristics, i.e., WAT browning, effectively inhibits obesity. Dai-Zong-Fang (DZF), a traditional Chinese medicine formula, has long been used to treat metabolic syndrome and obesity. This study aimed to explore the pharmacological mechanism of DZF against obesity.

Methods:In vivo, C57BL/6J mice were fed high-fat diets to establish the diet-induced obese (DIO) model. DZF (0.40 g/kg and 0.20 g/kg) and metformin (0.15 g/kg, positive control drug) were used as intervention drugs for six weeks, respectively. The effects of DZF on body size, blood glucose and lipid level, structure and morphology of adipocytes and browning of inguinal WAT (iWAT) in DIO mice were observed. In vitro, mature 3T3-L1 adipocytes were used as the model. Concentrations of DZF (0.8 mg/mL and 0.4 mg/mL) were selected according to the Cell Counting Kit-8 (CCK8). After 2d intervention, lipid droplet morphology was observed by BODIPY493/503 staining, and mitochondria number was observed by mito-tracker Green staining. H-89 dihydrochloride, a PKA inhibitor, was used to observe the change in browning markers′ expression. The expression levels of browning markers UCP1 and PGC-1α and key molecules of PKA pathway were detected in vivo and in vitro.

Results:In vivo, compared with vehicle control group, 0.40 g/kg DZF significantly reduced obesity in DIO mice from body weight, abdomen circumference, Lee′s index, and WAT/body weight (p < 0.01 or p < 0.001). 0.40 g/kg DZF also significantly reduced fasting blood glucose (FBG), serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (p < 0.01 or p < 0.001). The iWAT′s morphology and mitochondria were browning after DZF intervention. In HE-staining, the lipid droplets became smaller, and the number of mitochondria increased. The mitochondrial structure was remodeled under the electron microscope. The expression of UCP1, PGC-1α and PKA was elevated in iWAT detected by RT-qPCR (p < 0.05 or p < 0.001). In vitro, compared with the control group, 0.8 mg/mL DZF intervention significantly increased the number of mitochondria and expression of UCP1, PGC-1α, PKA, and pCREB (p < 0.05 or p < 0.01). In contrast, UCP1 and PGC-1α expression were significantly reversed after adding PKA inhibitor H-89 dihydrochloride.

Conclusion: DZF can promote UCP1 expression by activating the PKA pathway, thereby promoting browning of WAT, attenuating obesity, and reducing obesity-related glucose and lipid metabolism abnormalities, indicating that DZF has the potential to be selected as an anti-obesity drug to benefit obese patients.
Detection of herpes simplex virus in oral tongue squamous cell carcinoma
Authors: Koivikko Tiina , Rodrigues Priscila Campioni , Vehviläinen Mari , Hyvönen Petra , Sundquist Elias , Arffman Riikka K. , Al-Samadi Ahmed , Välimaa Hanna , Salo Tuula , Risteli Maija
Published: May 2023

Introduction: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. Contradictory results have been observed on the involvement of herpes simplex virus 1 (HSV-1) in oral squamous cell carcinomas. Here, we aimed to study the predominance of HSV-1 or HSV-2 in oral HSV infections and to investigate the presence of HSV-1 in OTSCC and its effect on carcinoma cell viability and invasion.

Methods: The distribution of HSV types one and two in diagnostic samples taken from suspected oral HSV infections was determined from the Helsinki University Hospital Laboratory database. We then analysed 67 OTSCC samples for HSV-1 infection using immunohistochemical staining. We further tested the effects of HSV-1 using six concentrations (0.00001–1.0 multiplicity of infection [MOI]) on viability and two concentrations (0.001 and 0.1 MOI) on invasion of highly invasive metastatic HSC-3 and less invasive primary SCC-25 OTSCC cell lines using MTT and Myogel-coated Transwell invasion assays.

Results: Altogether 321 oropharyngeal samples were diagnosed positive for HSV during the study period. HSV-1 was the predominant (97.8%) HSV type compared with HSV-2 (detected in 2.2% of samples). HSV-1 was also detected in 24% of the OTSCC samples and had no association with patient survival or recurrence. OTSCC cells were viable even after 6 days with low viral load (0.00001, 0.0001, 0.001 MOI) of HSV-1. In both cell lines, 0.001 MOI did not affect cell invasion. However, 0.1 MOI significantly reduced cell invasion in HSC-3 cells.

Discussion: HSV-1 infection is predominant compared with HSV-2 in the oral cavity. HSV-1 is detected in OTSCC samples without clinical significance, and OTSCC cell survival or invasion was not affected at low doses of HSV-1.