bluuebunny/crossref_metadata_2025 huggingface dataset:
Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells
Authors: Pecci Adali , Ogara María Florencia , Sanz Rosario T. , Vicent Guillermo Pablo
Published: November 2022

Steroid hormone receptors (SHRs) belong to a large family of ligand-activated nuclear receptors that share certain characteristics and possess others that make them unique. It was thought for many years that the specificity of hormone response lay in the ligand. Although this may be true for pure agonists, the natural ligands as progesterone, corticosterone and cortisol present a broader effect by simultaneous activation of several SHRs. Moreover, SHRs share structural and functional characteristics that range from similarities between ligand-binding pockets to recognition of specific DNA sequences. These properties are clearly evident in progesterone (PR) and glucocorticoid receptors (GR); however, the biological responses triggered by each receptor in the presence of its ligand are different, and in some cases, even opposite. Thus, what confers the specificity of response to a given receptor is a long-standing topic of discussion that has not yet been unveiled. The levels of expression of each receptor, the differential interaction with coregulators, the chromatin accessibility as well as the DNA sequence of the target regions in the genome, are reliable sources of variability in hormone action that could explain the results obtained so far. Yet, to add further complexity to this scenario, it has been described that receptors can form heterocomplexes which can either compromise or potentiate the respective hormone-activated pathways with its possible impact on the pathological condition. In the present review, we summarized the state of the art of the functional cross-talk between PR and GR in breast cancer cells and we also discussed new paradigms of specificity in hormone action.
Multiscale entropy and small-world network analysis in rs-fMRI — new tools to evaluate early basal ganglia dysfunction in diabetic peripheral neuropathy
Authors: Yuan Geheng , Zheng Yijia , Wang Ye , Qi Xin , Wang Rui , Ma Zhanyang , Guo Xiaohui , Wang Xiaoying , Zhang Jue
Published: November 2022

Objective

The risk of falling increases in diabetic peripheral neuropathy (DPN) patients. As a central part, Basal ganglia play an important role in motor and balance control, but whether its involvement in DPN is unclear.

Methods

Ten patients with confirmed DPN, ten diabetes patients without DPN, and ten healthy age-matched controls(HC) were recruited to undergo magnetic resonance imaging(MRI) to assess brain structure and zone adaptability. Multiscale entropy and small-world network analysis were then used to assess the complexity of the hemodynamic response signal, reflecting the adaptability of the basal ganglia.

Results

There was no significant difference in brain structure among the three groups, except the duration of diabetes in DPN patients was longer (p < 0.05). The complexity of basal ganglia was significantly decreased in the DPN group compared with the non-DPN and HC group (p < 0.05), which suggested their poor adaptability.

Conclusion

In the sensorimotor loop, peripheral and early central nervous lesions exist simultaneously in DPN patients. Multiscale Entropy and Small-world Network Analysis could detect basal ganglia dysfunction prior to structural changes in MRI, potentially valuable tools for early non-invasive screening and follow-up.
Agricultural carbon emission efficiency evaluation and influencing factors in Zhejiang province, China
Authors: Li Jingjie , Li Shanwei , Liu Qian , Ding Junli
Published: November 2022

Based on the classic IPCC carbon emission calculation theory, this paper calculates the agricultural carbon emissions intensity and efficiency in Zhejiang Province from 2011 to 2020. The LMDI model is further adapted to carry out the influence factors of agricultural carbon emissions. In addition, the grey prediction model GM (1, 1) is used to predict the carbon emissions of Zhejiang Province from 2022 to 2025. The results show that the agricultural carbon emissions and carbon emission intensity in Zhejiang Province have a downward trend. Further, it is concluded that Shaoxing, Hangzhou, Jiaxing, and Huzhou are the cities with low emission and high efficiency, and Wenzhou is the city with high emission and low efficiency. Meanwhile, the improvement of Total Factor Productivity (TFP) results from the joint action of Technical Progress Efficiency (TECH) and Technical Efficiency (EFF). TECH is greater than EFF, and Scale Efficiency (SE) and Pure Technical Efficiency (PTE) contributions change with the years. In general, the contribution of PTE is more significant than that of SE, and its improvement mainly rests on technical progress. Among the factors influencing agricultural carbon emission efficiency, agricultural carbon emission intensity and labor force size have inhibiting effects on agricultural carbon emission efficiency growth. In contrast, agricultural industrial structure, economic development, and urbanization positively affect agricultural carbon emission efficiency. The prediction results show that the overall carbon emissions of Zhejiang Province will get a downward trend. Finally, based on these findings, we offer policy implications.
Automatic differentiation and the optimization of differential equation models in biology
Authors: Frank Steven A.
Published: November 2022

A computational revolution unleashed the power of artificial neural networks. At the heart of that revolution is automatic differentiation, which calculates the derivative of a performance measure relative to a large number of parameters. Differentiation enhances the discovery of improved performance in large models, an achievement that was previously difficult or impossible. Recently, a second computational advance optimizes the temporal trajectories traced by differential equations. Optimization requires differentiating a measure of performance over a trajectory, such as the closeness of tracking the environment, with respect to the parameters of the differential equations. Because model trajectories are usually calculated numerically by multistep algorithms, such as Runge-Kutta, the automatic differentiation must be passed through the numerical algorithm. This article explains how such automatic differentiation of trajectories is achieved. It also discusses why such computational breakthroughs are likely to advance theoretical and statistical studies of biological problems, in which one can consider variables as dynamic paths over time and space. Many common problems arise between improving success in computational learning models over performance landscapes, improving evolutionary fitness over adaptive landscapes, and improving statistical fits to data over information landscapes.
There and back again: A meta-analytical approach on the influence of acclimation and altitude in the upper thermal tolerance of amphibians and reptiles
Authors: Carilo Filho Leildo M. , Gomes Lidiane , Katzenberger Marco , Solé Mirco , Orrico Victor G. D.
Published: November 2022

Realistic predictions about the impacts of climate change onbiodiversity requires gathering ecophysiological data and the critical thermal maxima (CTMax) is the most frequently used index to assess the thermal vulnerability of species. In the present study, we performed a systematic review to understand how acclimation and altitude affect CTMax estimates for amphibian and non-avian reptile species. We retrieved CTMax data for anurans, salamanders, lizards, snakes, and turtles/terrapins. Data allowed to perform a multilevel random effects meta-analysis to answer how acclimation temperature affect CTMax of Anura, Caudata, and Squamata and also meta-regressions to assess the influence of altitude on CTMax of frogs and lizards. Acclimation temperature influenced CTMax estimates of tadpoles, adult anurans, salamanders, and lizards, but not of froglets. In general, the increase in acclimation temperature led to higher CTMax values. Altitudinal bioclimatic gradient had an inverse effect for estimating the CTMax of lizards and anuran amphibians. For lizards, CTMax was positively influenced by the mean temperature of the wettest quarter. For anurans, the relationship is inverse; we recover a trend of decreasing CTMax when max temperature of warmest month and precipitation seasonality increase. There is an urgent need for studies to investigate the thermal tolerance of subsampled groups or even for which we do not have any information such as Gymnophiona, Serpentes, Amphisbaena, and Testudines. Broader phylogenetic coverage is mandatory for more accurate analyses of macroecological and evolutionary patterns for thermal tolerance indices as CTMax.
Establishing a database for sickle cell disease patient mapping and survival tracking: The sickle pan-african research consortium Nigeria example
Authors: Nnodu Obiageli , Madu Anazoeze , Chianumba Reuben , Isa Hezekiah Alkali , Olanrewaju Isaac , Osagie Samuel , Oyekanmi Nash , Sangeda Raphael Zozimus , Stewart Annemie , Nembaware Victoria , Morrice Jack , Jonas Mario , Mazandu Gaston , Wonkam Ambroise , Owolabi Olumide
Published: November 2022

Background: The Sickle Pan-African Research Consortium (SPARCO) and Sickle Africa Data Coordinating Center (SADaCC) were set up with funding from the US National Institute of Health (NIH) for physicians, scientists, patients, support groups, and statisticians to collaborate to reduce the high disease burden and alleviate the impact of Sickle Cell Disease (SCD) in Africa. For 5 years, SPARCO and SADaCC have been collecting basic clinical and demographic data from Nigeria, Tanzania, and Ghana. The resulting database will support analyses to estimate significant clinical events and provide directions for targeting interventions and assessing their impacts.

Method: The Nigerian study sited at Centre of Excellence for Sickle Cell Disease Research and Training (CESRTA), University of Abuja, adopted REDCap for online database management. The case report form (CRF) was adapted from 1,400 data elements adopted by SPARCO sites. It captures 215 data elements of interest across sub-sites, i.e., demographic, social, diagnostic, clinical, laboratory, imaging, and others. These were harmonized using the SADaCC data dictionary. REDCap was installed on University of Abuja cloud server at https://www.redcap.uniabuja.edu.ng. Data collected at the sites are sent to CESRTA for collation, cleaning and uploading to the database.

Results: 7,767 people living with sickle cell disease were enrolled at 25 health institutions across the six zones in Nigeria with 5,295 having had at least one follow-up visit with their clinical data updated. They range from 44 to 1,180 from 3 centers from South East, 4 from South, 5 from South West, 8 from North Central, 4 in North West and 3 in the North East. North West has registered 1,383 patients, representing 17.8%; North East, 359 (4.6%); North Central, 2,947 (37.9%); South West, 1,609 (20.7%); South, 442 (5.7%) and South East, 1,027 patients (13.2%).

Conclusion: The database is being used to support studies including analysis of clinical phenotypes of SCD in Nigeria, and evaluation of Hydroxyurea use in SCD. Reports undergoing review in journals have relied on the ease of data access in REDCap. The database is regularly updated by batch and individual record uploads while we are utilizing REDCap’s in-built functions to generate simple statistic.
Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report
Authors: Al-Jaberi Fatima A. H. , Crone Cornelia Geisler , Lindenstrøm Thomas , Arildsen Nicolai Skovbjerg , Lindeløv Emilia Sæderup , Aagaard Louise , Gravesen Eva , Mortensen Rasmus , Andersen Aase Bengaard , Olgaard Klaus , Hjaltelin Jessica Xin , Brunak Søren , Bonefeld Charlotte Menné , Kongsbak-Wismann Martin , Geisler Carsten
Published: November 2022

Tuberculosis (TB) presents a serious health problem with approximately a quarter of the world’s population infected with Mycobacterium tuberculosis (M. tuberculosis) in an asymptomatic latent state of which 5–10% develops active TB at some point in their lives. The antimicrobial protein cathelicidin has broad antimicrobial activity towards viruses and bacteria including M. tuberculosis. Vitamin D increases the expression of cathelicidin in many cell types including macrophages, and it has been suggested that the vitamin D-mediated antimicrobial activity against M. tuberculosis is dependent on the induction of cathelicidin. However, unraveling the immunoregulatory effects of vitamin D in humans is hampered by the lack of suitable experimental models. We have previously described a family in which members suffer from hereditary vitamin D-resistant rickets (HVDRR). The family carry a mutation in the DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional VDR, meaning that vitamin D cannot exert its effect in family members homozygous for the mutation. Studies of HVDRR patients open unique possibilities to gain insight in the immunoregulatory roles of vitamin D in humans. Here we describe the impaired ability of macrophages to produce cathelicidin in a HVDRR patient, who in her adolescence suffered from extrapulmonary TB. The present case is a rare experiment of nature, which illustrates the importance of vitamin D in the pathophysiology of combating M. tuberculosis.
Resveratrol ameliorates oxidative stress, inflammatory response and lipid metabolism in common carp (Cyprinus carpio) fed with high-fat diet
Authors: Wu Di , Li Jinnan , Fan Ze , Wang Liansheng , Zheng Xianhu
Published: November 2022

High-fat diet is regarded as crucial inducers of oxidative stress, inflammation, and metabolic imbalance. In order to investigate the ameliorative potential of resveratrol against the progression of liver injury towards steatohepatitis, common carp (Cyprinus carpio) were distributed into six experimental groups and were fed with a normal-fat diet, a high-fat diet, and supplemented with resveratrol (0.8, 1.6, 2.4, and 3.2 g/kg diet) for 8 weeks. The high-fat diet decreased the antioxidant capacities, as well as causing the inflammatory response and lipid deposition of common carp. Resveratrol induced a marked elevation in the final body weight, weight gain rate, condition factor and significant decrease in the feed conversion ratio. Moreover, dietary resveratrol showed a significant decrease in the alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein levels, which was accompanied by an increase in high-density lipoprotein concentration in serum. A significant elevation in total superoxide dismutase, catalase, glutathione peroxidase and a decreased malondialdehyde content were observed, along with a substantial elevation in antioxidant activities were found. Additionally, fish fed with resveratrol had an up-regulation of hepatic catalase, copper, zinc superoxide dismutase, glutathione peroxidase 1a, and glutathione peroxidase 1b gene expression via Nrf2 signaling pathway. Expectedly, our results also demonstrated that resveratrol regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (acetyl-CoA carboxylase 1, fatty acid synthase, and sterol regulatory element binding protein 1), fatty acid uptake-related genes of lipoprotein lipase, and β-oxidation-related genes via PPAR-γ signaling pathway. Furthermore, dietary resveratrol reduced inflammation, as evident by down-regulating the interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α expression levels and upregulating the interleukin-10 and transforming growth factor-β2 expression levels via NF-κB signaling pathway. As a whole, our results demonstrated that resveratrol defensed the impacts against high-fat diet on the serum biochemical, hepatic antioxidants, inflammation, and lipid metabolism.
Mesenchymal stromal cell extracellular vesicles for multiple sclerosis in preclinical rodent models: A meta-analysis
Authors: Xun Chengfeng , Deng Huiyin , Zhao Jing , Ge Lite , Hu Zhiping
Published: November 2022

Introduction

Extracellular vesicles (EVs), especially mesenchymal stem (stromal) cell-derived EVs (MSC-EVs), have gained attention as potential novel treatments for multiple sclerosis (MS). However, their effects remain incompletely understood. Thus, the purpose of this meta-analysis was to systematically review the efficacy of MSC-EVs in preclinical rodent models of MS.

Methods

We searched PubMed, EMBASE, and the Web of Science databases up to August 2021 for studies that reported the treatment effects of MSC-EVs in rodent MS models. The clinical score was extracted as an outcome. Articles were peer-reviewed by two authors based on the inclusion and exclusion criteria. This meta-analysis was conducted using Stata 15.1 and R.

Results

A total of twelve animal studies met the inclusion criteria. In our study, the MSC-EVs had a positive overall effect on the clinical score with a standardized mean difference (SMD) of -2.17 (95% confidence interval (CI)):-3.99 to -0.34, P = 0.01). A significant amount of heterogeneity was observed among the studies.

Conclusions

This meta-analysis suggests that transplantation of MSC-EVs in MS rodent models improved functional recovery. Additionally, we identified several critical knowledge gaps, such as insufficient standardized dosage units and uncertainty regarding the optimal dose of MSC-EVs transplantation in MS. These gaps must be addressed before clinical trials can begin with MSC-EVs.
Investigation of corrugated profiles in thin lossy dielectric slabs for wideband absorption up to 100 GHz
Authors: Huynen Isabelle
Published: November 2022

The paper compares and optimizes through modeling conductive polymer composite slabs having different architectures of corrugated surfaces, designed to minimize both the reflectivity and its sensitivity to the angle of incidence of a microwave/millimeter wave signal impinging on the corrugated surface of the slab. Simulations using CST Studio software consider Poly-Lactid-Acid as dielectric material since it is widely used for 3D printing and offers very good possibilities of recycling in the frame of sustainability and green processing. Various profiles of corrugation are investigated; triangular, sinusoidal, or square-dot profiles, and compared with a uniform profile. Parameters such as height, width, and periodicity of the corrugations are varied in order to optimize the performances in terms of reflectivity over a large range of frequencies, between 20 GHz and 100 GHz. The configuration considered is the reflective screen, when the corrugated lossy dielectric slab covers a metallic plate mimicking the target. The goal is to maintain the reflectivity below 10 dB, in order to ensure up to 95% of absorption, for incidence angles up to 60°. Guidelines for the design and optimization of corrugated dielectric slab absorbers are proposed using specific gauges (Rozanov formalism and figure of merit) for the assessment of performances. Particular attention is devoted to the feasibility of manufacturing corrugated structures using additive 3D printing techniques.
Biocontrol of strawberry gray mold caused by Botrytis cinerea with the termite associated Streptomyces sp. sdu1201 and actinomycin D
Authors: Yong Daojing , Li Yue , Gong Kai , Yu Yingying , Zhao Shuai , Duan Qiong , Ren Cailing , Li Aiying , Fu Jun , Ni Jinfeng , Zhang Youming , Li Ruijuan
Published: November 2022

Strawberry gray mold caused by Botrytis cinerea is one of the most severe diseases in pre- and post-harvest periods. Although fungicides have been an effective way to control this disease, they can cause serious “3R” problems (Resistance, Resurgence and Residue). In this study, Streptomyces sp. sdu1201 isolated from the hindgut of the fungus-growing termite Odontotermes formosanus revealed significant antifungal activity against B. cinerea. Four compounds (1–4) were isolated from Streptomyces sp. sdu1201 and further identified as actinomycins by the HRMS and 1D NMR data. Among them, actinomycin D had the strongest inhibitory activity against B. cinerea with the EC50 value of 7.65 μg mL−1. The control effect of actinomycin D on strawberry gray mold was also tested on fruits and leaves in vitro, and its control efficiency on leaves was 78.77% at 3 d. Moreover, actinomycin D can also inhibit the polarized growth of germ tubes of B. cinerea. Therefore, Streptomyces sp. sdu1201 and actinomycin D have great potential to gray mold as biocontrol agents.
Abundant bacteria shaped by deterministic processes have a high abundance of potential antibiotic resistance genes in a plateau river sediment
Authors: Zhao Yuhong , Lin Hui , Liu Yi , Jiang Ying , Zhang Weihong
Published: November 2022

Recent research on abundant and rare bacteria has expanded our understanding of bacterial community assembly. However, the relationships of abundant and rare bacteria with antibiotic resistance genes (ARGs) remain largely unclear. Here, we investigated the biogeographical patterns and assembly processes of the abundant and rare bacteria from river sediment at high altitudes (Lhasa River, China) and their potential association with the ARGs. The results showed that the abundant bacteria were dominated by Proteobacteria (55.4%) and Cyanobacteria (13.9%), while the Proteobacteria (33.6%) and Bacteroidetes (18.8%) were the main components of rare bacteria. Rare bacteria with a large taxonomic pool can provide function insurance in bacterial communities. Spatial distribution of persistent abundant and rare bacteria also exhibited striking differences. Strong selection of environmental heterogeneity may lead to deterministic processes, which were the main assembly processes of abundant bacteria. In contrast, the assembly processes of rare bacteria affected by latitude were dominated by stochastic processes. Abundant bacteria had the highest abundance of metabolic pathways of potential drug resistance in all predicted functional genes and a high abundance of potential ARGs. There was a strong potential connection between these ARGs and mobile genetic elements, which could increase the ecological risk of abundant taxa and human disease. These results provide insights into sedimental bacterial communities and ARGs in river ecosystems.
The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction
Authors: Dai Pei , Yu Hui-xian , Wang Zhao-xia , Liu Si-hao , Xu Guang-qing
Published: November 2022

Background and purpose

Extracranial artery stenosis (ECAS) is associated with the presence of individual markers of cerebral small vessel disease (CSVD). Here, we investigated the relationship between severe extracranial artery stenosis or occlusion and CSVD in patients with large artery atherosclerotic (LAA) cerebral infarction.

Methods

A total of 128 patients with LAA cerebral infarction who met our specific inclusion criteria were selected, including 92 males and 36 females. These patients were divided into three groups based on whether they had severe symptomatic extracranial arterial stenosis or occlusion, severe asymptomatic extracranial artery stenosis or occlusion, or severe extracranial artery stenosis or occlusion (both symptomatic and asymptomatic). Intra-group comparisons were then performed to examine whether there were any differences in the total CSVD scores and Fazekas scores.

Results

Patients with severe extracranial arterial stenosis or occlusion and those with severe asymptomatic extracranial arterial stenosis or occlusion had a significantly higher total CSVD score (P < 0.05), but there were no significant differences between the groups in terms of Fazekas scores. Furthermore, there were no significant difference in the total CSVD scores and Fazekas scores when compared between patients with or without severe symptomatic extracranial arterial stenosis or occlusion.

Conclusion

Severe stenosis or occlusion of the contralateral extracranial artery may increase the incidence of CSVD in patients with LAA cerebral infarction. Active and effective clinical intervention following comprehensive evaluation should be undertaken for unilateral cerebral infarction patients with severe stenosis or occlusion of the contralateral extracranial arterial.
Therapeutic strategies for intracerebral hemorrhage
Authors: Li Zhe , Khan Suliman , Liu Yang , Wei Ruixue , Yong V. Wee , Xue Mengzhou
Published: November 2022

Stroke is the second highest cause of death globally, with an increasing incidence in developing countries. Intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. ICH is associated with poor neurological outcomes and high mortality due to the combination of primary and secondary injury. Fortunately, experimental therapies are available that may improve functional outcomes in patients with ICH. These therapies targeting secondary brain injury have attracted substantial attention in their translational potential. Here, we summarize recent advances in therapeutic strategies and directions for ICH and discuss the barriers and issues that need to be overcome to improve ICH prognosis.
Peri-procedure efficacy and safety of one-stop hybrid surgery for the treatment of brain arteriovenous malformations: A single-center preliminary experience
Authors: Fang Wei , Yang Zijian , Liu Yufeng , Yu Jia , Sun Peng , Zhao Zhenwei , He Yue , Zhang Tao , Deng Jianping
Published: November 2022

Background

Some deficiencies and shortcomings in treatment strategies of brain arteriovenous malformation (bAVM) remain. It is worth exploring whether the one-stop hybrid surgical platform can play a positive role in the treatment of bAVM.

Objective

This study investigated short clinical and angiographic results of one-stop hybrid surgery for the treatment of bAVM.

Methods

All patients with bAVM treated with one-stop hybrid surgery were reviewed from February 2017 to December 2021. Data including demographic information, clinical conditions, characteristics of AVM, procedure details, and clinical and angiographic results were collected.

Result

In total, 150 cerebral bAVM patients received one-stop hybrid surgery; among them, 122 received surgical resection assisted by intraoperative DSA, and 28 were treated with combination surgical resection and endovascular embolization. Complete angiographic obliteration of the AVM was achieved in 136 patients (90.7%), and procedure-related death and neurological deficit rates were 7.3%. Of all relevant variables, logistic regression analysis showed that the Spetzler & Martin (S&M) score was the only factor related to the cure rate (P < 0.001) and endpoint complication rate (P = 0.007).

Conclusions

In our preliminary experience, one-stop hybrid surgery for the treatment of brain AVMs achieves a high angiographic total occlusion rate, with acceptable peri-procedure morbidity and mortality. For S&M 4 and 5 lesions, more cases and further study are needed to investigate the effects and safety of hybrid surgery.
Medical management of cerebral edema in large hemispheric infarcts
Authors: DeHoff Grace , Lau Winnie
Published: November 2022

Acute ischemic stroke confers a high burden of morbidity and mortality globally. Occlusion of large vessels of the anterior circulation, namely the intracranial carotid artery and middle cerebral artery, can result in large hemispheric stroke in ~8% of these patients. Edema from stroke can result in a cascade effect leading to local compression of capillary perfusion, increased stroke burden, elevated intracranial pressure, herniation and death. Mortality from large hemispheric stroke is generally high and surgical intervention may reduce mortality and improve good outcomes in select patients. For those patients who are not eligible candidates for surgical decompression either due timing, medical co-morbidities, or patient and family preferences, the mainstay of medical management for cerebral edema is hyperosmolar therapy. Other neuroprotectants for cerebral edema such as glibenclamide are under investigation. This review will discuss current guidelines and evidence for medical management of cerebral edema in large hemispheric stroke as well as discuss important neuromonitoring and critical care management targeted at reducing morbidity and mortality for these patients.
Abnormal proximal-distal interactions in upper-limb of stroke survivors during object manipulation: A pilot study
Authors: Phan Thanh , Nguyen Hien , Vermillion Billy C. , Kamper Derek G. , Lee Sang Wook
Published: November 2022

Despite its importance, abnormal interactions between the proximal and distal upper extremity muscles of stroke survivors and their impact on functional task performance has not been well described, due in part to the complexity of upper extremity tasks. In this pilot study, we elucidated proximal–distal interactions and their functional impact on stroke survivors by quantitatively delineating how hand and arm movements affect each other across different phases of functional task performance, and how these interactions are influenced by stroke. Fourteen subjects, including nine chronic stroke survivors and five neurologically-intact subjects participated in an experiment involving transport and release of cylindrical objects between locations requiring distinct proximal kinematics. Distal kinematics of stroke survivors, particularly hand opening, were significantly affected by the proximal kinematics, as the hand aperture decreased and the duration of hand opening increased at the locations that requires shoulder abduction and elbow extension. Cocontraction of the extrinsic hand muscles of stroke survivors significantly increased at these locations, where an increase in the intermuscular coherence between distal and proximal muscles was observed. Proximal kinematics of stroke survivors was also affected by the finger extension, but the cocontraction of their proximal muscles did not significantly increase, suggesting the changes in the proximal kinematics were made voluntarily. Our results showed significant proximal-to-distal interactions between finger extension and elbow extension/shoulder abduction of stroke survivors exist during their functional movements. Increased cocontraction of the hand muscles due to increased neural couplings between the distal and proximal muscles appears to be the underlying mechanism.
Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis
Authors: Melamed Esther , Palmer Jamie L. , Fonken Cara
Published: November 2022

Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.
RNA biomarkers for alcohol use disorder
Authors: Ferguson Laura B. , Mayfield R. Dayne , Messing Robert O.
Published: November 2022

Alcohol use disorder (AUD) is highly prevalent and one of the leading causes of disability in the US and around the world. There are some molecular biomarkers of heavy alcohol use and liver damage which can suggest AUD, but these are lacking in sensitivity and specificity. AUD treatment involves psychosocial interventions and medications for managing alcohol withdrawal, assisting in abstinence and reduced drinking (naltrexone, acamprosate, disulfiram, and some off-label medications), and treating comorbid psychiatric conditions (e.g., depression and anxiety). It has been suggested that various patient groups within the heterogeneous AUD population would respond more favorably to specific treatment approaches. For example, there is some evidence that so-called reward-drinkers respond better to naltrexone than acamprosate. However, there are currently no objective molecular markers to separate patients into optimal treatment groups or any markers of treatment response. Objective molecular biomarkers could aid in AUD diagnosis and patient stratification, which could personalize treatment and improve outcomes through more targeted interventions. Biomarkers of treatment response could also improve AUD management and treatment development. Systems biology considers complex diseases and emergent behaviors as the outcome of interactions and crosstalk between biomolecular networks. A systems approach that uses transcriptomic (or other -omic data, e.g., methylome, proteome, metabolome) can capture genetic and environmental factors associated with AUD and potentially provide sensitive, specific, and objective biomarkers to guide patient stratification, prognosis of treatment response or relapse, and predict optimal treatments. This Review describes and highlights state-of-the-art research on employing transcriptomic data and artificial intelligence (AI) methods to serve as molecular biomarkers with the goal of improving the clinical management of AUD. Considerations about future directions are also discussed.
In silico investigation of molecular networks linking gastrointestinal diseases, malnutrition, and sarcopenia
Authors: Hoch Matti , Ehlers Luise , Bannert Karen , Stanke Christina , Brauer David , Caton Vanessa , Lamprecht Georg , Wolkenhauer Olaf , Jaster Robert , Wolfien Markus
Published: November 2022

Malnutrition (MN) is a common primary or secondary complication in gastrointestinal diseases. The patient’s nutritional status also influences muscle mass and function, which can be impaired up to the degree of sarcopenia. The molecular interactions in diseases leading to sarcopenia are complex and multifaceted, affecting muscle physiology, the intestine (nutrition), and the liver at different levels. Although extensive knowledge of individual molecular factors is available, their regulatory interplay is not yet fully understood. A comprehensive overall picture of pathological mechanisms and resulting phenotypes is lacking. In silico approaches that convert existing knowledge into computationally readable formats can help unravel mechanisms, underlying such complex molecular processes. From public literature, we manually compiled experimental evidence for molecular interactions involved in the development of sarcopenia into a knowledge base, referred to as the Sarcopenia Map. We integrated two diseases, namely liver cirrhosis (LC), and intestinal dysfunction, by considering their effects on nutrition and blood secretome. We demonstrate the performance of our model by successfully simulating the impact of changing dietary frequency, glycogen storage capacity, and disease severity on the carbohydrate and muscle systems. We present the Sarcopenia Map as a publicly available, open-source, and interactive online resource, that links gastrointestinal diseases, MN, and sarcopenia. The map provides tools that allow users to explore the information on the map and perform in silico simulations.
An exploration into the application of specialty-orientated CBL pedagogy in undergraduate teaching in pediatric surgery
Authors: Ma Wenyue , Gao Hongjie , Liu Xiaoya , Chang Mengmeng , Jia Changlin , Sun Fengyin
Published: November 2022

Objective

This study aims to identify whether the specialty-oriented case-based learning (CBL) pedagogy contributes to the teaching of basic theory and practical operation in undergraduate clinical teaching in pediatric surgery, and to assess the satisfaction of undergraduates.

Methods

A total of 72 undergraduates in Grade 2016 who interned at Qilu Hospital of Shandong University were enrolled in this study. All these undergraduates voluntarily participated in this experimental study. They were randomly divided into the experimental group (the CBL group, n = 36) and the control group [the traditional lecture-based learning (LBL) group, n = 36] with the assistance of random number tables. In the control group, a traditional pedagogy was adopted and the knowledge in the textbook was explained according to the syllabus. In the experimental group, a specialty-oriented CBL pedagogy was adopted under the guidance of clinical instructors. After the teaching, a comparison was drawn between both groups in respect of the theoretical exam and practical exam scores. In addition, the teaching results were evaluated by a questionnaire survey.

Results

The average theoretical exam scores and comprehensive scores of undergraduates in the CBL group were higher than those in the LBL group (P < 0.05). There was no significant difference in the practical exam scores between the CBL group and the LBL group (P > 0.05). However, those undergraduates in the CBL group attained higher scores in doctor-patient communication and perioperative diagnosis and treatment (P < 0.05). According to the questionnaire survey, the undergraduates in the CBL group had higher satisfaction than those in the LBL group. Besides, this specialty-oriented CBL pedagogy had higher performance in improving their ability to solve problems independently and cultivating and expanding their knowledge compared with the traditional pedagogy. Meanwhile, this specialty-oriented CBL pedagogy can cultivate the critical thinking of undergraduates, which could increase their learning efficiency and improve their interest in learning.

Conclusion

This specialty-oriented CBL pedagogy could improve the mastery of professional knowledge, course satisfaction, doctor-patient communication ability in clinical practice, and perioperative diagnosis and treatment ability of these undergraduates. Therefore, it is worthwhile to recommend and popularize this pedagogy in undergraduate clinical teaching in pediatric surgery.
Supercritical fluid extract of Angelica sinensis promotes the anti-colorectal cancer effect of oxaliplatin
Authors: Hao Doudou , Liu Jia , Guo Ziyou , Chen Jiajia , Li Tingting , Li Xin , Mei Kai , Wang Lingmin , Wang Xinyi , Wu Qing
Published: November 2022

Oxaliplatin-based chemotherapy regimens are recommended for patients with advanced colorectal cancer (CRC). However, oxaliplatin (OXA) can cause toxic side effects at the recommended dosage. Therefore, it is necessary to find new drug candidates that can synergize with OXA and thereby lower the OXA dose while still maintaining its efficacy. Angelica sinensis is a common drug in traditional Chinese medicine and has demonstrated a significant anti-CRC effect in modern pharmacological studies. The active ingredients in Angelica sinensis can be effectively extracted by a supercritical fluid extract. In this study, the supercritical fluid extract of Angelica sinensis (A-SFE) was obtained by a stable extraction process and was chemically characterized by GC/MS. The anti-cancer effect of A-SFE when applied individually was explored in vitro through MTT, scratch, and Transwell assay. The effect of A-SFE on CRC cells under the influence of tumor-associated macrophages (TAMs) was explored by a co-culture model. The results showed that A-SFE could inhibit the viability, metastasis, and invasion of HCT116 cells, especially under the influence of TAMs. When 20–100 μg/ml of A-SFE and 8–64 μg/ml of OXA were used in combination in HCT116 cells, synergistic or additive effects were shown in different concentration combinations. The CT26 syngeneic mouse model was used to explore the anti-CRC effect of OXA combined with A-SFE in vivo. The tumor volume, expression levels of Ki67, MMP9, and CD206 in the OXA + A-SFE group were less than those in the OXA group. In conclusion, A-SFE has the potential to become an adjuvant drug for OXA in the treatment of CRC, which provides new strategies for anti-colorectal cancer research.
SIRT1 activation and its effect on intercalated disc proteins as a way to reduce doxorubicin cardiotoxicity
Authors: Podyacheva Ekaterina , Toropova Yana
Published: November 2022

According to the World Health Organization, the neoplasm is one of the main reasons for morbidity and mortality worldwide. At the same time, application of cytostatic drugs like an independent type of cancer treatment and in combination with surgical methods, is often associated with the development of cardiovascular complications both in the early and in the delayed period of treatment. Doxorubicin (DOX) is the most commonly used cytotoxic anthracycline antibiotic. DOX can cause both acute and delayed side effects. The problem is still not solved, as evidenced by the continued activity of researchers in terms of developing approaches for the prevention and treatment of cardiovascular complications. It is known, the heart muscle consists of cardiomyocytes connected by intercalated discs (ID), which ensure the structural, electrical, metabolic unity of the heart. Various defects in the ID proteins can lead to the development of cardiovascular diseases of various etiologies, including DOX-induced cardiomyopathy. The search for ways to influence the functioning of ID proteins of the cardiac muscle can become the basis for the creation of new therapeutic approaches to the treatment and prevention of cardiac pathologies. SIRT1 may be an interesting cardioprotective variant due to its wide functional significance. SIRT1 activation triggers nuclear transcription programs that increase the efficiency of cellular, mitochondrial metabolism, increases resistance to oxidative stress, and promotes cell survival. It can be assumed that SIRT1 can not only provide a protective effect at the cardiomyocytes level, leading to an improvement in mitochondrial and metabolic functions, reducing the effects of oxidative stress and inflammatory processes, but also have a protective effect on the functioning of IDs structures of the cardiac muscle.
Anticholinesterase activity of Areca Catechu: In Vitro and in silico green synthesis approach in search for therapeutic agents against Alzheimer’s disease
Authors: Pradeep Sushma , Prabhuswaminath Samudyata C. , Reddy Pruthvish , Srinivasa Sudhanva M. , Shati Ali A. , Alfaifi Mohammad Y. , Eldin I. Elbehairi Serag , Achar Raghu Ram , Silina Ekaterina , Stupin Victor , Manturova Natalia , Glossman-Mitnik Daniel , Shivamallu Chandan , Kollur Shiva Prasad
Published: November 2022

For many years, the primary focus has been on finding effective treatments for Alzheimer’s disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant speciesAreca CatechuL. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15–20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs.In vitroanti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizingin silicoresearch. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.
Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis
Authors: Zeng Wanying , Liu Xiaojing , Wu Yangyang , Cai Yuting , Li Zhennan , Ye Fei , Sun Yuanhong , Li Feng , Xing Huijie , Wang Shuai
Published: November 2022

Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the most important phase II mechanisms, facilitating drug clearance via conjugation of glucuronic acid with polar groups of xenobiotics. Accumulating evidence suggests that IBDs impact drug disposition, but whether and how IBDs regulate UGTs and drug glucuronidation remains undefined. In this study, we aim to investigate the expression of UGTs and drug glucuronidation in experimental colitis. Given that glucuronidation occurs primarily in the liver, we analyzed the mRNA changes in hepatic UGTs with a DSS-induced mouse colitis model. Twelve UGTs were downregulated in the liver of colitis mice including UGT1A1 and UGT1A9 (two representative UGTs). Colitis in mice downregulated UGT1A1 and UGT1A9 in the liver but not in small intestine, colon, and kidney. We also established that the downregulation of UGTs was attributed to the disease itself rather than the DSS compound. Moreover, colitis-reduced UGT1A1 and UGT1A9 lead to dampened baicalein and puerarin glucuronidation. PXR was the only UGT regulator significantly downregulated in colitis mice, suggesting dysregulation of PXR is associated with the downregulation of UGT1A1 and UGT1A9, thereby potentially resulting in dysfunction of baicalein and puerarin glucuronidation. Collectively, we establish that UGTs and glucuronidation are dysregulated in colitis, and this effect may cause variation in drug responsiveness in IBDs.
Sulfur-containing amino acids and their metabolites in atrial fibrosis
Authors: Wang Rui , Qi Yong Fen , Ding Chun Hua , Zhang Da
Published: November 2022

Atrial fibrosis, a symbol of atrial structural remodelling, is a complex process involved in the occurrence and maintenance of atrial fibrillation (AF). Atrial fibrosis is regulated by multiple factors. Sulfur containing amino acids and their metabolites, such as hydrogen sulfide (H2S) and taurine, can inhibit the process of atrial fibrosis and alleviate atrial remodeling. However, homocysteine can promote the activation of atrial fibroblasts and further promote atrial fibrosis. In this review, we will focus on the recent progress in atrial structural changes and molecular mechanisms of atrial fibrosis, as well as the regulatory roles and possible mechanisms of sulfur containing amino acids and their metabolites in atrial fibrosis. It is expected to provide new ideas for clarifying the mechanism of atrial fibrosis and finding targets to inhibit the progress of atrial fibrosis.