bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy With Suicide: A Bibliometrics Study and Visualization Analysis via CiteSpace
Authors: Guo Yi , Xu Zheng-Yan-Ran , Cai Meng-Ting , Gong Wen-Xin , Shen Chun-Hong
Published: January 2022

Objective:

The purpose of this study was to analyze the research status of epilepsy with suicide and to determine the hotspots and frontiers via CiteSpace.

Method:

We searched the Web of Science Core Collection (WoSCC) for studies related to epilepsy and suicide from inception to September 30, 2021. We used CiteSpace to generate online maps of collaboration between countries, institutions, and authors, and revealed hot spots and frontiers in epilepsy with suicide.

Results:

A total of 631 publications related to epilepsy with suicide were retrieved from the WoSCC. Andres M. Kanner was the most published author (25 papers). The USA and Columbia University were the leading country and institution in this field, with 275 and 25 papers, respectively. There were active cooperation between institutions, countries, and authors. Hot topics focused on depression, antiseizure medications, pediatric epilepsy, and risk factors of suicide in patients with epilepsy (PWEs).

Conclusions:

Based on the CiteSpace findings, this study detected active collaboration among countries, institutions and authors. The main current research trends include suicide caused by depression, suicide caused by the use of antiseizure medications, suicide in children with epilepsy, and risk factors for suicide in PWEs. Thus, more attention should be paid to the psychiatric comorbidity of PWEs (especially pediatric epilepsy), the suicidal tendency of PWEs, and the rational use of antiseizure medications in the future.
Mini Review: Impedance Measurement in Neuroscience and Its Prospective Application in the Field of Surgical Neurooncology
Authors: Abboud Tammam , Mielke Dorothee , Rohde Veit
Published: January 2022

Impedance measurement of human tissue can be performed either in vivo or ex vivo. The majority of the in-vivo approaches are non-invasive, and few are invasive. To date, there is no gold standard for impedance measurement of intracranial tissue. In addition, most of the techniques addressing this topic are still experimental and have not found their way into clinical practice. This review covers available impedance measurement approaches in the neuroscience in general and specifically addresses recent advances made in the application of impedance measurement in the field of surgical neurooncology. It will provide an understandable picture on impedance measurement and give an overview of limitations that currently hinders clinical application and require future technical and conceptual solutions.
The Control of Movements via Motor Gamma Oscillations
Authors: Ulloa José Luis
Published: January 2022

The ability to perform movements is vital for our daily life. Our actions are embedded in a complex environment where we need to deal efficiently in the face of unforeseen events. Neural oscillations play an important role in basic sensorimotor processes related to the execution and preparation of movements. In this review, I will describe the state of the art regarding the role of motor gamma oscillations in the control of movements. Experimental evidence from electrophysiological studies has shown that motor gamma oscillations accomplish a range of functions in motor control beyond merely signaling the execution of movements. However, these additional aspects associated with motor gamma oscillation remain to be fully clarified. Future work on different spatial, temporal and spectral scales is required to further understand the implications of gamma oscillations in motor control.
Auditory Brain Stem Responses in the C57BL/6J Fragile X Syndrome-Knockout Mouse Model
Authors: Chawla Amita , McCullagh Elizabeth A.
Published: January 2022

Sensory hypersensitivity, especially in the auditory system, is a common symptom in Fragile X syndrome (FXS), the most common monogenic form of intellectual disability. However, linking phenotypes across genetic background strains of mouse models has been a challenge and could underly some of the issues with translatability of drug studies to the human condition. This study is the first to characterize the auditory brain stem response (ABR), a minimally invasive physiological readout of early auditory processing that is also used in humans, in a commonly used mouse background strain model of FXS, C57BL/6J. We measured morphological features of pinna and head and used ABR to measure the hearing range, and monaural and binaural auditory responses in hemizygous males, homozygous females, and heterozygous females compared with those in wild-type mice. Consistent with previous study, we showed no difference in morphological parameters across genotypes or sexes. There was no significant difference in hearing range between the sexes or genotypes, however there was a trend towards high frequency hearing loss in male FXS mice. In contrast, female mice with homozygous FXS had a decreased amplitude of wave IV of the monaural ABR, while there was no difference in males for amplitudes and no change in latency of ABR waveforms across sexes and genotypes. Finally, males with FXS had an increased latency of the binaural interaction component (BIC) at 0 interaural timing difference compared with that in wild-type males. These findings further clarify auditory brain stem processing in FXS by adding more information across genetic background strains allowing for a better understanding of shared phenotypes.
Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study - GEMS-I
Authors: Ngwa Julius S. , Nwulia Evaristus , Ntekim Oyonumo , Bedada Fikru B. , Kwabi-Addo Bernard , Nadarajah Sheeba , Johnson Steven , Southerland William M. , Kwagyan John , Obisesan Thomas O.
Published: January 2022

Background

DNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers.

Design

Elderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO2max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants.

Results

Eleven MCI participants (aerobic: 73% females; mean age 72.3 ± 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 ± 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO2max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 × 10–26), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value < 10–5, include hypomethylations of SCARB1 (8.8 × 10–25), ARTN (6.1 × 10–25), NR1H2 (2.1 × 10–18) and PPP2R5D (9.8 × 10–18).

Conclusion

We conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.
Multisensory Integration: Is Medial Prefrontal Cortex Signaling Relevant for the Treatment of Higher-Order Visual Dysfunctions?
Authors: Skirzewski Miguel , Molotchnikoff Stéphane , Hernandez Luis F. , Maya-Vetencourt José Fernando
Published: January 2022

In the mammalian brain, information processing in sensory modalities and global mechanisms of multisensory integration facilitate perception. Emerging experimental evidence suggests that the contribution of multisensory integration to sensory perception is far more complex than previously expected. Here we revise how associative areas such as the prefrontal cortex, which receive and integrate inputs from diverse sensory modalities, can affect information processing in unisensory systems via processes of down-stream signaling. We focus our attention on the influence of the medial prefrontal cortex on the processing of information in the visual system and whether this phenomenon can be clinically used to treat higher-order visual dysfunctions. We propose that non-invasive and multisensory stimulation strategies such as environmental enrichment and/or attention-related tasks could be of clinical relevance to fight cerebral visual impairment.
F-18 FDG PET/CT Imaging in Normal Variants, Pitfalls and Artifacts in the Abdomen and Pelvis
Authors: Vangu Mboyo D. T. , Momodu Jaleelat I.
Published: January 2022

Since its introduction into clinical practice, multimodality imaging has revolutionized diagnostic imaging for both oncologic and non-oncologic pathologies. 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging which takes advantage of increased anaerobic glycolysis that occurs in tumor cells (Warburg effect) has gained significant clinical relevance in the management of most, if not all oncologic conditions. Because FDG is taken by both normal and abnormal tissues, PET/CT imaging may demonstrate several normal variants and imaging pitfalls. These may ultimately impact disease detection and diagnostic accuracy. Imaging specialists (nuclear medicine physicians and radiologists) must demonstrate a thorough understanding of normal and physiologic variants in the distribution of 18F-FDG; including potential imaging pitfalls and technical artifacts to minimize misinterpretation of images. The normal physiologic course of 18F-FDG results in a variable degree of uptake in the stomach, liver, spleen, small and large bowel. Urinary excretion results in renal, ureteric, and urinary bladder uptake. Technical artifacts can occur due to motion, truncation as well as the effects of contrast agents and metallic hardware. Using pictorial illustrations, this paper aims to describe the variants of physiologic 18F-FDG uptake that may mimic pathology as well as potential benign conditions that may result in misinterpretation of PET/CT images in common oncologic conditions of the abdomen and pelvis.
Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis
Authors: Chen Dexin , Wang Hong , Xin Xing , Zhang Long , Yu Aihong , Li Shuwen , He Rongxia
Published: January 2022

Objective

Calcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium.

Method

Eight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0–1.49 g), and the low-dose group (<1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia.

Results and Discussion

A total of 48 studies were incorporated into the final analyses. All doses of calcium supplementation reduced the incidence of gestational hypertension in the low-risk population (low dose - three studies; medium dose- 11 studies; high dose- 28 studies), whereas the medium-dose (three studies) reduced the incidence of gestational hypertension in high-risk groups. Moreover, a medium dose of calcium supplementation had the maximum effect in reducing gestational hypertension in low-risk and high-risk populations. The medium (three studies) and high doses (13 studies) of calcium supplementation reduced the incidence of pre-eclampsia in the low-risk groups. However, a medium-dose calcium supplementation maximally prevented pre-eclampsia in the low-risk population. The authenticity and reliability of the results were reduced due to the limitations of contemporary studies in terms of experimental design, result measurement, statistics, and evidence quality. Therefore, high-quality studies with larger sample size are required to evaluate further the effect of calcium supplementation in preventing gestational hypertension and pre-eclampsia.
Lipid Changes During Endocrine Therapy in Breast Cancer Patients: The Results of a 5-Year Real-World Retrospective Analysis
Authors: He Tao , Li Xu , Li Jiayuan , Wang Zhu , Fan Yuan , Li Xiusong , Fu Zhoukai , Wu Yunhao , Lv Qing , Luo Ting , Zhong Xiaorong , Chen Jie
Published: January 2022

Background

The aim of this study was to investigate the status of serum lipids during endocrine therapy.

Methods

We retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy.

Results

For premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p<0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p<0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p<0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years.

Conclusions

TAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.
Progression-Free Survival as Early Efficacy Endpoint in Resectable Esophageal Cancer Treated With Neoadjuvant Therapy: A Systematic Review
Authors: Zhu Jie , Tao Jin , Dai Zhen , Tan Yan , Jiang Li , Wang Qifeng , Lang Jinyi
Published: January 2022

To investigate literature-based evidence regarding progression-free survival (PFS) as an early efficacy endpoint in patients with resectable esophageal or gastroesophageal junction (GEJ) cancer receiving neoadjuvant therapy, this study identified large-scale randomized controlled trials (RCTs) with strict quality control. Twenty-four RCTs involving 7,514 patients were included. Trial-level correlation analysis was conducted to analyze the relationship between PFS hazard ratio (HR) and overall survival (OS) HR, Δ median PFS and Δ median OS. Correlation analysis at the neoadjuvant treatment arm level was performed between 1- to 5-year PFS and 5-year OS, median PFS and median OS. Subgroup analysis was performed in patients treated with standard neoadjuvant chemoradiotherapy (NCRT). The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. In trial-level correlation, PFS were strongly associated with OS HR (r, 0.82 [95% confidence interval (CI), 0.42-0.97]) and Δ median survival (r, 0.83 [95% CI, 0.54-0.96]). In neoadjuvant treatment arms, there was a strong correlation between 1 to 5-year PFS rates and 5-year OS (r, 0.83-0.95), and median PFS and median OS (r, 0.97 [95% CI, 0.85-0.99]). NCRT subgroup analysis demonstrated acceptable consistency. In conclusion, we recommend PFS as an early efficacy endpoint in resected esophageal or GEJ cancer treated with neoadjuvant therapy.
In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China
Authors: Li Yiqun , Abudureheiyimu Nilupai , Mo Hongnan , Guan Xiuwen , Lin Shaoyan , Wang Zijing , Chen Yimeng , Chen Shanshan , Li Qiao , Cai Ruigang , Wang Jiayu , Luo Yang , Fan Ying , Yuan Peng , Zhang Pin , Li Qing , Ma Fei , Xu Binghe
Published: January 2022

Background

To characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.

Methods

The China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).

Results

There were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p < 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).

Conclusion

Our findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.
Multi-Omics Profiling Suggesting Intratumoral Mast Cells as Predictive Index of Breast Cancer Lung Metastasis
Authors: Zhang Leyi , Pan Jun , Wang Zhen , Yang Chenghui , Chen Wuzhen , Jiang Jingxin , Zheng Zhiyuan , Jia Fang , Zhang Yi , Jiang Jiahuan , Su Ke , Ren Guohong , Huang Jian
Published: January 2022

Breast cancer lung metastasis has a high mortality rate and lacks effective treatments, for the factors that determine breast cancer lung metastasis are not yet well understood. In this study, data from 1067 primary tumors in four public datasets revealed the distinct microenvironments and immune composition among patients with or without lung metastasis. We used multi-omics data of the TCGA cohort to emphasize the following characteristics that may lead to lung metastasis: more aggressive tumor malignant behaviors, severer genomic instability, higher immunogenicity but showed generalized inhibition of effector functions of immune cells. Furthermore, we found that mast cell fraction can be used as an index for individual lung metastasis status prediction and verified in the 20 human breast cancer samples. The lower mast cell infiltrations correlated with tumors that were more malignant and prone to have lung metastasis. This study is the first comprehensive analysis of the molecular and cellular characteristics and mutation profiles of breast cancer lung metastasis, which may be applicable for prognostic prediction and aid in choosing appropriate medical examinations and therapeutic regimens.
The Role of miR-4256/HOXC8 Signaling Axis in the Gastric Cancer Progression: Evidence From lncRNA-miRNA-mRNA Network Analysis
Authors: Gu Haijuan , Zhong Yuejiao , Liu Jibin , Shen Qian , Wei Rong , Zhu Haixia , Zhang Xunlei , Xia Xianxian , Yao Min , Ni Meixin
Published: January 2022

Gastric cancer is a deadly human malignancy and the molecular mechanisms underlying gastric cancer pathophysiology are very complicated. Thus, further investigations are warranted to decipher the underlying molecular mechanisms. With the development of high-throughput screening and bioinformatics, gene expression profiles with large scale have been performed in gastric cancer. In the present study, we mined The Cancer Genome Atlas (TCGA) database and analyzed the gene expression profiles between gastric cancer tissues and normal gastric tissues. A series of differentially expressed lncRNAs, miRNAs and mRNAs between gastric cancer tissues and normal gastric tissues were identified. Based on the differentially expressed genes, we constructed miRNA-mRNA network, lncRNA-mRNA network and transcriptional factors-mRNA-miRNA-lncRNA network. Furthermore, the Kaplan survival analysis showed that high expression levels of EVX1, GBX2, GCM1, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12 and HOXC13 were all significantly correlated with shorter overall survival of the patients with gastric cancer. On the other hand, low expression level of HOXA13 was associated with shorter overall survival of patients with gastric cancer. Among these hub genes, we performed the in vitro functional studies of HOXC8 in the gastric cancer cells. Knockdown of HOXC8 and overexpression of miR-4256 both significantly repressed the gastric cancer cell proliferation and migration, and miR-4256 repressed the expression of HOXC8 via targeting its 3’ untranslated region in gastric cancer cells. Collectively, our results revealed that a complex interaction networks of differentially expressed genes in gastric cancer, and further functional studies indicated that miR-4256/HOXC8 may be an important axis in regulating gastric cancer progression.
PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination
Authors: Qiu Wenjin , Cai Xiaomin , Xu Kaya , Song Shibin , Xiao Zumu , Hou Yunan , Qi Xiaolan , Liu Feng , Chen Yimin , Yang Hua , Chu Liangzhao , Liu Jian
Published: January 2022

Regenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positively correlated with the tumor grade. Consistently, ectopic expression of PRL1 in glioma cell lines significantly enhanced their tumorigenicity and invasion both in vitro and in vivo by promoting epithelial-mesenchymal transition (EMT). Conversely, knocking down PRL1 blocked EMT in GBM cells, and inhibited their invasion, migration and tumorigenic growth. Additionally, PRL1 also stabilized Snail2 through its deubiquitination by activating USP36, thus revealing Snail2 as a crucial mediator of the oncogenic effects of PRL1 in GBM pathogenesis. Finally, PRL1 protein levels were positively correlated with that of Snail2 and predicted poor outcome of GBMs. Collectively, our data support that PRL1 promotes GBM progression by activating USP36-mediated Snail2 deubiquitination. This novel PRL1/USP36/Snail2 axis may be a promising therapeutic target for glioblastoma.
Taiwan Society of Colon and Rectum Surgeons (TSCRS) Consensus for Anti-Inflammatory Nutritional Intervention in Colorectal Cancer
Authors: Ma Cheng-Jen , Hu Wan-Hsiang , Huang Meng-Chuan , Chiang Jy-Ming , Hsieh Pao-Shiu , Wang Huann-Sheng , Chiang Chien-Ling , Hsieh Hui-Min , Chen Chou-Chen , Wang Jaw-Yuan
Published: January 2022

Malnutrition and systemic inflammatory response (SIR) frequently occur in patients with colorectal cancer (CRC) and are associated with poor prognosis. Anti-inflammatory nutritional intervention is not only a way to restore the malnourished status but also modulate SIR. Nine experts, including colorectal surgeons, physicians and dieticians from 5 hospitals geographically distributed in Taiwan, attended the consensus meeting in Taiwan Society of Colon and Rectum Surgeons for a 3-round discussion and achieved the consensus based on a systematic literature review of clinical studies and published guidelines. The consensus recommends that assessment of nutritional risk and SIR should be performed before and after CRC treatment and appropriate nutritional and/or anti-inflammatory intervention should be adapted and provided accordingly.
Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia
Authors: Zhang Jiaxu , Luo Yi , Feng Mingxuan , Xia Qiang
Published: January 2022

Background: Biliary atresia (BA) is one of the most common and fatal abnormalities of newborns. Increasing evidences indicated that immunology was the critical part of the etiology. This research used a public gene expression database to explore the immune microenvironment of BA liver.

Methods: The gene expression profiles GSE46960, GSE159720, and GSE15235, containing BA and normal liver gene expression data, were obtained from the Expression Omnibus Gene. We applied CIBERSORTx to quantify 22 subsets of immune cells in BA liver. The differentially expressed genes (DEGs) and immune cells were used to further explore their relationship with liver fibrosis and the inflammation status of BA.

Results: The expression of immune-related genes CXCL6, CXCL8, CXCL10, CCL20, IL32, TGFB2, SPP1, and SLIT2 was significantly different between BA and normal liver, among which CXCL8 was the hub gene. Six of 22 immune cell proportions were significantly different between BA and normal liver. Specifically, M0 macrophages and resting memory CD4+ T cells were upregulated in BA liver compared with normal liver. Meanwhile, monocytes, resting natural killer (NK) cells, plasma cells, and regulatory T (Treg) cells were downregulated. A further correlation analysis revealed that SLIT2 and CXCL6 owned high positive correlation coefficients with fibrosis grade, while the proportion of resting NK cells was negatively correlated. Proportions of resting CD4+ memory T cells were strongly related to the inflammation grade of BA liver.

Conclusion: Biliary atresia is a disease strongly correlated with immune response. Our results might provide a clue for further exploration of BA etiology, which may promote a potential prediction model based on immune infiltration features.
Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial
Authors: Lee Su Won , Lyu Yee Ran , Kim Si Yeon , Yang Won Kyung , Kim Seung Hyung , Kim Ki Mo , Chae Sung-Wook , Kang Weechang , Jung In Chul , Park Yang Chun
Published: January 2022

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study.

Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].
New Oral Anticoagulants for Venous Thromboembolism Prophylaxis in Total Hip and Knee Arthroplasty: A Systematic Review and Network Meta-Analysis
Authors: Yi Yi-hu , Gong Song , Gong Tian-lun , Zhou Ling-yun , Hu Can , Xu Wei-hua
Published: January 2022

Background:There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA).

Methods:We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA).

Results:25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days.

Conclusion:Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890].
Laser Photobiomodulation 808 nm: Effects on Gene Expression in Inflammatory and Osteogenic Biomarkers in Human Dental Pulp Stem Cells
Authors: Rocha Elaine A. da , Alvarez Marcela M. P. , Pelosine Agatha M. , Carrilho Marcela Rocha O. , Tersariol Ivarne L. S. , Nascimento Fábio D.
Published: January 2022

The tissue engineering of dental oral tissue is tackling significant advances and the use of stem cells promises to boost the therapeutical approaches of regenerative dentistry. Despite advances in this field, the literature is still scarce regarding the modulatory effect of laser photobiomodulation (PBM) on genes related to inflammation and osteogenesis in Postnatal Human Dental Pulp Stem cells (DPSCs). This study pointedly investigated the effect of PBM treatment in proliferation, growth and differentiation factors, mineralization, and extracellular matrix remodeling genes in DPSCs. Freshly extracted human third molars were used as a source for DPSCs isolation. The isolated DPSCs were stimulated to an inflammatory state, using a lipopolysaccharide (LPS) model, and then subjected or not to laser PBM. Each experiment was statistically evaluated according to the sample distribution. A total of 85 genes related to inflammation and osteogenesis were evaluated regarding their expression by RT-PCR. Laser PBM therapy has shown to modulate several genes expression in DPSCs. PBM suppressed the expression of inflammatory gene TNF and RANKL and downregulated the gene expression for VDR and proteolytic enzymes cathepsin K, MMP-8 and MMP-9. Modulation of gene expression for proteinase-activated receptors (PARs) following PBM varied among different PARs. As expected, PBM blocked the odontoblastic differentiation of DPSCs when subjected to LPS model. Conversely, PBM has preserved the odontogenic potential of DPSCs by increasing the expression of TWIST-1/RUNEX-2/ALP signaling axis. PBM therapy notably played a role in the DPSCs genes expression that mediate inflammation process and tissue mineralization. The present data opens a new perspective for PBM therapy in mineralized dental tissue physiology.
Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
Authors: Zhu Xiaofei , Li Teng , Hu En , Duan Lihua , Zhang Chunhu , Wang Yang , Tang Tao , Yang Zhaoyu , Fan Rong
Published: January 2022

Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored.

Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San.

Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting.

Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting.

Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San.
DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells
Authors: Zhang Xuguang , Zhang Yuxin , Zhou Mingyan , Xie Yiqiang , Dong Xiujuan , Bai Feihu , Zhang Junqing
Published: January 2022

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.
Culinary Spices in Food and Medicine: An Overview of Syzygium aromaticum (L.) Merr. and L. M. Perry [Myrtaceae]
Authors: Otunola Gloria Aderonke
Published: January 2022

Spices-dried aromatic parts of plants (leaves, seeds, bark, roots, rhizomes, buds, etc) used to enhance flavour, taste and colour (sensory quality) of foods, are increasingly finding other useful roles in healthcare beyond their primary use as culinary organoleptic enhancers. Several spices are currently being investigated for their potential health benefits, because of the failing efficacy, toxicity and high cost associated with conventional drugs. One such spice:Syzygium aromaticum(L.) Merr. and L.M.Perry [Myrtaceae] (Clove), has a multi-dimensional role in diet, medicine, functional foods and nutraceuticals, agriculture, among other industries. Peer-reviewed articles, mostly from PubMed and Google Scholar, were consulted for the purpose of this review. The nutritional and phytochemical contents, selected biological activities as well as some functional foods and beverages of clove and their uses for human health are presented. Although these observations are largely empirical, the efficacious attributes have led to their pharmacological applications in the indigenous system of medicine all over the world and bridge between food, diet and medicine. Considering the GRAS status of clove, more studies on bioavailability, accumulation, toxicity, dosage and efficacy of clove as a spice drug or functional foods in biological systems especially in humans are required. Meanwhile, clove and its products can be used as co-adjuvants in the prevention, treatment and management of chronic diseases. Further, many applications of clove in food, health, cosmetics, pharmaceutics, nanoparticles and agricultural industries are still open for investigations.
Phytochemical Analysis, Antioxidant and Bone Anabolic Effects of Blainvillea acmella (L.) Philipson
Authors: Abdul Rahim Rohanizah , Jayusman Putri Ayu , Lim Vuanghao , Ahmad Nor Hazwani , Abdul Hamid Zuratul Ain , Mohamed Sharlina , Muhammad Norliza , Ahmad Fairus , Mokhtar Norfilza , Mohamed Norazlina , Shuid Ahmad Nazrun , Naina Mohamed Isa
Published: January 2022

Blainvillea acmella (L.) Philipson [Asteraceae] (B. acmella) is an important medicinal plant native to Brazil, and it is widely known as a toothache plant. A plethora of studies have demonstrated the antioxidant activities of B. acmella and few studies on the stimulatory effects on alkaline phosphatase (ALP) secretion from bone cells; however, there is no study on its antioxidant and anabolic activity on bone cells. The study aimed to evaluate the phytochemical contents of aqueous and ethanol extracts of B. acmella using gas chromatography mass spectrometry (GCMS) and liquid chromatography time of flight mass spectrometry (LCTOFMS) along with the total phenolic (TPC) and flavonoid (TFC) contents using Folin-Ciocalteu and aluminum colorimetric methods. The extracts of B. acmella leaves were used to scavenge synthetic-free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The bone anabolic effects of B. acmella extracts on MC3T3-E1 cells were measured with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoium bromide (MTT) at 1, 3, 5, and 7 days, Sirius-red and ALP at 7 and 14 days, and Alizarin Red S at 14 and 21 days. Comparatively, ethanol extract of B. acmella (BaE) contributed higher antioxidant activities (IC50 of 476.71 µg/ml and 56.01 ± 6.46 mg L-ascorbic acid/g against DPPH and FRAP, respectively). Anabolic activities in bone proliferation, differentiation, and mineralization were also higher in B. acmella of ethanol (BaE) than aqueous (BaA) extracts. Positive correlations were observed between phenolic content (TPC and TFC) to antioxidant (ABTS and FRAP) and anabolic activities. Conversely, negative correlations were present between phenolic content to antioxidant (DPPH) activity. These potential antioxidant and bone anabolic activities in BaE might be due to the phytochemicals confirmed through GCMS and LCTOFMS, revealed that terpenoids of α-cubebene, cryophyllene, cryophyllene oxide, phytol and flavonoids of pinostrobin and apigenin were the compounds contributing to both antioxidant and anabolic effects in BaE. Thus, B. acmella may be a valuable antioxidant and anti-osteoporosis agent. Further study is needed to isolate, characterize and elucidate the underlying mechanisms responsible for the antioxidant and bone anabolic effects.
Phytochemical Studies on Two Unexplored Endemic Medicinal Plants of India, Barleria terminalis and Calacanthus grandiflorus
Authors: Otari Shreedhar S. , Patel Suraj B. , Lekhak Manoj M. , Ghane Savaliram G.
Published: January 2022

Barleria terminalisNees andCalacanthus grandiflorus(Dalzell) Radlk. are endemic medicinal plants of the Western Ghats of India. The aim of the present research work was to investigate phytochemical profile, potent bioactives using RP-HPLC, LC-MS and GC-MS and to evaluate their bioactivities. Acetone was found to be the best extraction medium for separating phytochemicals. Similarly, acetone and methanol extracts exhibited potential antioxidant properties. Ethanol extract ofB. terminalisstem showed potent acetylcholinesterase (AChE) (89.10 ± 0.26%) inhibitory activity. Inhibition of α-amylase (36.96 ± 2.96%) activity was observed the best in ethanol extract ofB. terminalisleaves and α-glucosidase inhibitory activity (94.33 ± 0.73%) in ethanol extract ofC. grandiflorusstem. RP-HPLC analysis confirmed the presence of several phenolic compounds (gallic acid, hydroxybenzoic acid, vanillic acid, chlorogenic acid and coumaric acid) and phenylethanoid glycoside (verbascoside). The highest phenolics content were observed inB. terminalis(GA (4.17 ± 0.002), HBA (3.88 ± 0.001), VA (4.54 ± 0.001), CHLA (0.55 ± 0.004) mg/g DW, respectively). Similarly, LC-MS and GC-MS revealed the presence of phenolics, glycosides, terpenes, steroids, fatty acids, etc. Moreover, positive correlation between studied phytochemicals and antioxidants was observed in principal component analysis. Based on the present investigation, we conclude thatB. terminalisandC. grandifloruscan be further explored for their active principles particularly, phenylethanoid glycosides and iridoids and their use in drug industry for pharmaceutical purposes.
The Role and Application of Exosomes in Gastric and Colorectal Cancer
Authors: Li Qirong , Wang Dongxu , Ding Dayong , Feng Ye , Hou Ruizhi , Liu Dianfeng , Lin Chao , Gao Yongjian
Published: January 2022

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes—small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment.
Use of a Fission Yeast Platform to Identify and Characterize Small Molecule PDE Inhibitors
Authors: Hoffman Charles S.
Published: January 2022

Cyclic nucleotide phosphodiesterases (PDEs) have been proven to be targets for which highly selective and potent drugs can be developed. Mammalian genomes possess 21 genes whose products are pharmacologically grouped into 11 families; however related genes from pathogenic organisms display sufficient divergence from the mammalian homologs such that PDE inhibitors to these enzymes could be used to treat parasitic infections without acting on the related human PDEs. We have developed a platform for expressing cloned PDEs in the fission yeast Schizosaccharomyces pombe, allowing for inexpensive, but robust screening for small molecule inhibitors that are cell permeable. Such compounds typically display the expected biological activity when tested in cell culture, including anti-inflammatory properties for PDE4 and PDE7 inhibitors. The genetic pliability of S. pombe also allows for molecular genetic screens to identify mutations in target PDE genes that confer some resistance to these inhibitors as a way of investigating the PDE-inhibitor interaction. This screening method is readily accessible to academic laboratories as it does not require the purification of large quantities of a target protein. This allows for the discovery and profiling of PDE inhibitors to treat inflammation or of inhibitors of targets such as pathogen PDEs for which there may not be a sufficient financial motivation for pharmaceutical companies to identify selective PDE inhibitors using more traditional in vitro enzyme-based screening methods.