bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines
Authors: Thakur Suresh , Sasi Shalitha , Pillai Sindhu Gopinathan , Nag Ayantika , Shukla Dhananjay , Singhal Ritu , Phalke Sameer , Velu G. S. K.
Published: February 2022

With the high rate of COVID-19 infections worldwide, the emergence of SARS-CoV-2 variants was inevitable. Several mutations have been identified in the SARS-CoV-2 genome, with the spike protein as one of the mutational hot spots. Specific amino acid substitutions such as D614G and N501Y were found to alter the transmissibility and virulence of the virus. The WHO has classified the variants identified with fitness-enhancing mutations as variants of concern (VOC), variants of interest (VOI) or variants under monitoring (VUM). The VOCs pose an imminent threat as they exhibit higher transmissibility, disease severity and ability to evade vaccine-induced and natural immunity. Here we review the mutational landscape on the SARS-CoV-2 structural and non-structural proteins and their impact on diagnostics, therapeutics and vaccines. We also look at the effectiveness of approved vaccines, antibody therapy and convalescent plasma on the currently prevalent VOCs, which are B.1.17, B.1.351, P.1, B.1.617.2 and B.1.1.529. We further discuss the possible factors influencing mutation rates and future directions.
Alcohol-Related Elevation of Liver Transaminase Is Associated With Gut Microbiota in Male
Authors: Jiao Mengfan , Yan Su , Shi Qingmiao , Liu Ying , Li Yaoguang , Lv Jun , Ding Suying , Li Ang
Published: February 2022

Alcoholic liver damage has become a widespread health problem as alcohol consumption increases and is usually identified by elevated liver transaminase. We conducted this study to investigate the role of the gut microbiome in the individual susceptibility to alcoholic liver injury. We divided the participants into four groups based on alcohol consumption and liver transaminase elevation, which were drinking case group, drinking control group, non-drinking case group, and non-drinking control group. The drinking case group meant participants who were alcohol consumers with elevated liver transaminase. We found that alpha and beta diversities of the drinking case group differed from the other three groups. Species Faecalibacterium prausnitzii and Roseburia hominis were significantly in lower abundance in the drinking case group and were proved the protective effect against inflammatory liver damage in the former study. Ruminococcus gnavus exhibited the most positive association to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and contributed to liver inflammation.
Prospective Studies on the Risk of Rheumatoid Arthritis: The European Risk RA Registry
Authors: Studenic Paul , Hensvold Aase , Kleyer Arnd , van der Helm-van Mil Annette , Pratt Arthur G. , Sieghart Daniela , Krönke Gerhard , Williams Ruth , de Souza Savia , Karlfeldt Susanne , Johannesson Martina , Krogh Niels Steen , Klareskog Lars , Catrina Anca I.
Published: February 2022

Background

The accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the initiation of autoimmunity, and result in the formation of autoantibodies such as anti-citrullinated peptide antibodies (ACPA). In parallel, at-risk individuals may be asymptomatic or experience joint pain (arthralgia) that is itself non-specific or clinically suspicious for evolving RA, even in the absence of overt arthritis. Optimal strategies for the management of people at-risk of RA, both for symptom control and to delay or prevent progression to classifiable disease, remain poorly understood.

Methods

To help address this, groups of stakeholders from academia, clinical rheumatology, industry and patient research partners have collaborated to advance understanding, define and study different phases of the at-risk state. In this current report we describe different European initiatives in the field and the successful effort to build a European Registry of at-risk people to facilitate observational and interventional research.

Results

We outline similarities and differences between cohorts of at-risk individuals at institutions spanning several countries, and how to best combine them within the new database. Over the past 2 years, besides building the technical infrastructure, we have agreed on a core set of variables that all partners should strive to collect for harmonization purposes.

Conclusion

We emphasize to address this process from different angles and touch on the biologic, epidemiologic, analytic, and regulatory aspects of collaborative studies within a meta-database of people at-risk of RA.
Expression of MicroRNAs Is Dysregulated by HIV While Mycobacterium tuberculosis Drives Alterations of Small Nucleolar RNAs in HIV Positive Adults With Active Tuberculosis
Authors: Olsson Oskar , Tesfaye Fregenet , Søkilde Rolf , Mazurek Jolanta , Abebe Markos , Yeba Habtamu , Aseffa Abraham , Skogmar Sten , Balcha Taye Tolera , Rovira Carlos , Björkman Per , Jansson Marianne
Published: February 2022

HIV infection affects the course of tuberculosis (TB), and HIV and Mycobacterium tuberculosis (Mtb) synergize in disease progression through complex immunological interplay. To gain further understanding of these mechanisms, we compared the microRNA (miRNA) and small nucleolar RNA (snoRNA) expression patterns in whole blood of individuals with active TB, with and without HIV coinfection (HIV+/TB+ and HIV-/TB+), and HIV and TB-negative individuals (HIV-/TB-). We found that 218 miRNAs were differentially expressed between HIV+/TB+ and HIV-/TB+, while no statistically significant difference in snoRNA expression was observed between these groups. In contrast, both miRNA (n = 179) and snoRNA (n = 103) expression patterns were significantly altered in HIV+/TB+ individuals compared to those of the HIV-/TB- controls. Of note, 26 of these snoRNAs were also significantly altered between the HIV-/TB+ and HIV-/TB- groups. Normalization toward the miRNA and snoRNA expression patterns of the HIV-/TB- control group was noted during anti-TB and antiretroviral treatment in HIV+/TB+ participants. In summary, these results show that HIV coinfection influences miRNA expression in active TB. In contrast, snoRNA expression patterns differ between individuals with and without active TB, independently of HIV coinfection status. Moreover, in coinfected individuals, therapy-induced control of HIV replication and clearance of Mtb appears to normalize the expression of some small non-coding RNA (sncRNA). These findings suggest that dysregulation of miRNA is a mechanism by which HIV may modify immunity against TB, while active TB alters snoRNA expression. Improved understanding of how regulation of sncRNA expression influences the disease course in coinfected individuals may have implications for diagnostics, risk stratification, and host-directed therapy. Here, we propose a novel mechanism by which HIV alters the immune response to TB.
The Timing of Nitrogen Addition Impacts Yeast Genes Expression and the Production of Aroma Compounds During Wine Fermentation
Authors: Godillot Joséphine , Sanchez Isabelle , Perez Marc , Picou Christian , Galeote Virginie , Sablayrolles Jean-Marie , Farines Vincent , Mouret Jean-Roch
Published: February 2022

Among the different compounds present in the must, nitrogen is an essential nutrient for the management of fermentation kinetics but also plays an important role in the synthesis of fermentative aromas. To address the problems related to nitrogen deficiencies, nitrogen additions during alcoholic fermentation have been implemented. The consequences of such additions on the main reaction are well known. However, their impact on aromas synthesis is still poorly understood. So, the main objective of this study was to determine the impact of nitrogen addition during the stationary phase on both the fermentation kinetics and aroma synthesis. To reach this goal, we used a transdisciplinary approach combining statistical modeling (Box-Behnken design and response surface modeling) and gene expression study (transcriptomic analysis). Our results indicated that nitrogen metabolism, central carbon metabolism (CCM), fermentation kinetics and aroma production were significantly impacted by nitrogen addition. The most remarkable point was the different regulation of the bioconversion of higher alcohols into acetate esters on one hand and of fatty acids into ethyl esters on the other hand. We highlighted that the conversion of higher alcohols into acetate esters was maximum when nitrogen was added at the beginning of the stationary phase. Conversely, the highest conversion of acids into ethyl esters was reached when nitrogen was added close to the end of the stationary phase. Moreover, even if the key element in the production of these two ester families appeared to be the enzymatic activity responsible for their production, rather than the availability of the corresponding precursors, these enzymatic activities were differently regulated. For acetate esters, the regulation occurred at gene level: theATF2gene was overexpressed following nitrogen addition during the stationary phase. On the opposite, no induction of gene expression was noted for ethyl esters; it seemed that there was an allosteric regulation.
The Predictive Value of Individual Electric Field Modeling for Transcranial Alternating Current Stimulation Induced Brain Modulation
Authors: Preisig Basil C. , Hervais-Adelman Alexis
Published: February 2022

There is considerable individual variability in the reported effectiveness of non-invasive brain stimulation. This variability has often been ascribed to differences in the neuroanatomy and resulting differences in the induced electric field inside the brain. In this study, we addressed the question whether individual differences in the induced electric field can predict the neurophysiological and behavioral consequences of gamma band tACS. In a within-subject experiment, bi-hemispheric gamma band tACS and sham stimulation was applied in alternating blocks to the participants’ superior temporal lobe, while task-evoked auditory brain activity was measured with concurrent functional magnetic resonance imaging (fMRI) and a dichotic listening task. Gamma tACS was applied with different interhemispheric phase lags. In a recent study, we could show that anti-phase tACS (180° interhemispheric phase lag), but not in-phase tACS (0° interhemispheric phase lag), selectively modulates interhemispheric brain connectivity. Using a T1 structural image of each participant’s brain, an individual simulation of the induced electric field was computed. From these simulations, we derived two predictor variables: maximal strength (average of the 10,000 voxels with largest electric field values) and precision of the electric field (spatial correlation between the electric field and the task evoked brain activity during sham stimulation). We found considerable variability in the individual strength and precision of the electric fields. Importantly, the strength of the electric field over the right hemisphere predicted individual differences of tACS induced brain connectivity changes. Moreover, we found in both hemispheres a statistical trend for the effect of electric field strength on tACS induced BOLD signal changes. In contrast, the precision of the electric field did not predict any neurophysiological measure. Further, neither strength, nor precision predicted interhemispheric integration. In conclusion, we found evidence for the dose-response relationship between individual differences in electric fields and tACS induced activity and connectivity changes in concurrent fMRI. However, the fact that this relationship was stronger in the right hemisphere suggests that the relationship between the electric field parameters, neurophysiology, and behavior may be more complex for bi-hemispheric tACS.
Convergent and Divergent Structural Connectivity of Brain White Matter Network Between Patients With Erectile Dysfunction and Premature Ejaculation: A Graph Theory Analysis Study
Authors: Zhang Tielong , Yuan Peng , Cui Yonghua , Yuan Weibiao , Jiang Daye
Published: February 2022

Background

Sexual dysfunction, namely, erectile dysfunction (ED) and premature ejaculation (PE), has been found to be associated with abnormal structural connectivity in the brain. Previous studies have mainly focused on a single disorder, however, convergent and divergent structural connectivity patterns of the brain network between ED and PE remain poorly understood.

Methods

T1-weighted structural data and diffusion tensor imaging data of 28 patients with psychological ED, 28 patients with lifelong PE (LPE), and 28 healthy controls (HCs) were obtained to map the white matter (WM) brain networks. Then, the graph-theoretical method was applied to investigate the differences of network properties (small-world measures) of the WM network between patients with ED and LPE. Furthermore, nodal segregative and integrative parameters (nodal clustering coefficient and characteristic path length) were also explored between these patients.

Results

Small-world architecture of the brain networks were identified for both psychological ED and LPE groups. However, patients with ED exhibited increased average characteristic path length of the brain network when compared with patients with LPE and HCs. No significant difference was found in the average characteristic path length between patients with LPE and HCs. Moreover, increased nodal characteristic path length was found in the right middle frontal gyrus (orbital part) of patients with ED and LPE when compared with HCs. In addition, patients with ED had increased nodal characteristic path length in the right middle frontal gyrus (orbital part) when compared with patients with LPE.

Conclusion

Together, our results demonstrated that decreased integration of the right middle frontal gyrus (orbital part) might be a convergent neuropathological basis for both psychological ED and LPE. In addition, patients with ED also exhibited decreased integration in the whole WM brain network, which was not found in patients with LPE. Therefore, altered integration of the whole brain network might be the divergent structural connectivity patterns for psychological ED and LPE.
Quantitative Analysis for the Delineation of the Subthalamic Nuclei on Three-Dimensional Stereotactic MRI Before Deep Brain Stimulation Surgery for Medication-Refractory Parkinson’s Disease
Authors: Su Chun-Yu , Wong Alex Mun-Ching , Chang Chih-Chen , Tu Po-Hsun , Chen Chiung Chu , Yeh Chih-Hua
Published: February 2022

Delineation of the subthalamic nuclei (STN) on MRI is critical for deep brain stimulation (DBS) surgery in patients with Parkinson’s disease (PD). We propose this retrospective cohort study for quantitative analysis of MR signal-to-noise ratio (SNR), contrast, and signal difference-to-noise ratio (SDNR) of the STN on pre-operative three-dimensional (3D) stereotactic MRI in patients with medication-refractory PD. Forty-five consecutive patients with medication-refractory PD who underwent STN-DBS surgery in our hospital from January 2018 to June 2021 were included in this study. All patients had whole-brain 3D MRI, including T2-weighted imaging (T2WI), T2-weighted fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI), at 3.0 T scanner for stereotactic navigation. The signal intensities of the STN, corona radiata, and background noise were obtained after placing regions of interest (ROIs) on corresponding structures. Quantitative comparisons of SNR, contrast, and SDNR of the STN between MR pulse sequences, including the T2WI, FLAIR, and SWI. Subgroup analysis regarding patients’ sex, age, and duration of treatment. We used one-way repeated measures analysis of variance for quantitative comparisons of SNR, contrast, and SDNR of the STN between different MR pulse sequences, and we also used the dependent t-test for the post hoc tests. In addition, we used Mann–Whitney U test for subgroup analyses. Both the contrast (0.33 ± 0.07) and SDNR (98.65 ± 51.37) were highest on FLAIR (all p < 0.001). The SNR was highest on SWI (276.16 ± 115.5), and both the SNR (94.23 ± 31.63) and SDNR (32.14 ± 17.23) were lowest on T2WI. Subgroup analyses demonstrated significantly lower SDNR on SWI for patients receiving medication treatment for ≥13 years (p = 0.003). In conclusion, on 3D stereotactic MRI of medication-refractory PD patients, the contrast and SDNR for the STN are highest on FLAIR, suggesting the optimal delineation of STN on FLAIR.
Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia
Authors: Alharbi Norah , Matar Rawan , Cupler Edward , Al-Hindi Hindi , Murad Hatem , Alhomud Iftteah , Monies Dorota , Alshehri Ali , Alyahya Mossaed , Meyer Brian , Bohlega Saeed
Published: February 2022

Background

To characterize the phenotypic, neurophysiological, radiological, pathological, and genetic profile of 33 Saudi Arabian families with dysferlinopathy.

Methods

A descriptive observational study was done on a cohort of 112 Saudi Arabian families with LGMD. Screening for the Dysferlin (DYSF) gene was done in a tertiary care referral hospital in Saudi Arabia. Clinical, Neurophysiological, Radiological, Pathological, and Genetic findings in subjects with dysferlin mutation were the primary outcome variables. Statistical analysis was done by Epi-info.

Results

33 out of 112 families (29.46%) registered in the LGMD cohort had Dysferlinopathy. 53 subjects (28 males, 52.83%) from 33 families were followed up for various periods ranging from 1 to 28 years. The mean age of onset was 17.79 ± 3.48 years (Range 10 to 25 years). Miyoshi Myopathy phenotype was observed in 50.94% (27 out of 53), LGMDR2 phenotype in 30.19% (16 out of 53), and proximodistal phenotype in 15.09% (8 out of 53) of the subjects. Loss of ambulation was observed in 39.62% (21 out of 53 subjects). Electrophysiological, Radiological, and histopathological changes were compatible with the diagnosis. Mean serum Creatinine Kinase was 6,464.45 ± 4,149.24 with a range from 302 to 21,483 IU/L. In addition, 13 dysferlin mutations were identified two of them were compound heterozygous. One founder mutation was observed c.164_165insA in 19 unrelated families.

Conclusion

The prevalence of Dysferlinopathy was 29.46% in the native Saudi LGMD cohort. It is the most prevalent subtype seconded by calpainopathy. The clinical course varied among the study subjects and was consistent with those reported from different ethnic groups. One founder mutation was identified. Initial screening of the founder mutations in new families is highly recommended.
Health at Every Size®-Based Interventions May Improve Cardiometabolic Risk and Quality of Life Even in the Absence of Weight Loss: An Ancillary, Exploratory Analysis of the Health and Wellness in Obesity Study
Authors: Dimitrov Ulian Mariana , Pinto Ana Jéssica , Morais Sato Priscila de , Benatti Fabiana B. , Lopes de Campos-Ferraz Patricia , Coelho Desire , Roble Odilon J. , Sabatini Fernanda , Perez Isabel , Aburad Luiz , Vessoni André , Fernandez Unsain Ramiro , Rogero Marcelo Macedo , Sampaio Geni , Gualano Bruno , Scagliusi Fernanda B.
Published: February 2022

We examined whether weight loss following HAES®-based interventions associates with changes in cardiometabolic risk factors and quality of life of women with obesity. This was an exploratory, ancillary analysis of a 7-month, mixed-method, randomized controlled trial. Fifty-five women (age: 33.0 ± 7.2; BMI: 30–39.9 kg/m2) were included in this study. Body weight, cardiovascular risk factors, clustered cardiometabolic risk, and quality of life were assessed before (Pre) and after HAES®-based interventions (Post). Delta scores (Post-Pre) were calculated for each outcome and used in linear regression models. After adjusting by potential confounders, weight loss was associated with improvements in waist circumference (β = 0.83, p <0.001), fasting glycemia (β = 0.45, p = 0.036), total cholesterol (β = 1.48, p = 0.024), LDL (β = 1.33, p = 0.012), clustered cardiometabolic risk (β = 0.18, p = 0.006), and quality of life (β = −1.05, p = 0.007). All participants but one who reduced body weight (n = 11) improved clustered cardiometabolic risk and quality of life. Of relevance, 34% and 73% of the participants who maintained or gained weight improved clustered cardiometabolic risk and quality of life, respectively, although the magnitude of improvements was lower than that among those who lose weight. Improvements in cardiovascular risk factors and quality of life following HAES®-based interventions associated with weight loss as expected. However, most of the participants who maintained or even gained weight experienced benefits to some extent. This suggests that weight-neutral, lifestyle-modification interventions may improve wellness and health-related outcomes, even in the absence of weight loss.
Gut Microbiota and Immune Modulatory Properties of Human Breast Milk Streptococcus salivarius and S. parasanguinis Strains
Authors: Li Shuo , Li Na , Wang Chenwei , Zhao Yi , Cao Jie , Li Xuejing , Zhang Ziyi , Li Yue , Yang Xin , Wang Xiaoxin , Che Chuanyan , Zhao Yufeng , Wang Linghua , Zhao Liping , Shen Jian
Published: February 2022

Human breast milk Streptococcus spp. are transferred to infant guts via breast feeding, but their effects on the gut microbiota and immunity remain unclear. In this study, we characterized gut microbiota and immune modulatory properties of human breast milk S. salivarius F286 and S. parasanguinis F278 that had been shown to be able to colonize gut. The two Streptococcus strains were orally administered to mouse pups individually at 1 × 107 cells/day from postnatal Days 1 to 21. At postnatal week 3 (the weaning period), S. salivarius F286 reduced the colonic microbiota α-diversity, increased 21 amplicon sequence variants (ASVs), including bacteria from Akkermansia, Intestinimonas, and Lachnospiraceae, and decreased 52 ASVs, including bacteria from Eubacterium, Bifidobacterium, Escherichia-Shigella, and Turicibacter; however, S. parasanguinis F278 didn't change the colonic microbiota. Both Streptococcus strains reduced the ileal mRNA expression of cytokine/transcription factor representatives of T helper (Th) cells, including IFN-γ (Th1), Gata3 (Th2), and TGF-β (Treg) in 2-week-old suckling mice, and promoted the ileal expression of Foxp3 and TGF-β, which are representatives of anti-inflammatory Treg cells, in 3-week-old weaning mice. The two Streptococcus strains exhibited anti-inflammatory potential when incubated in vitro with human peripheral blood mononuclear cells and TNF-α-treated gut epithelial HT29 cells. In C. elegans, both strains activated immune response genes, which was associated with their lifespan-prolonging effects. Our results suggest that S. salivarius F286 and S. parasanguinis F278 may exert regulatory (anti-inflammatory) roles in gut immunity and S. salivarius F286 can modulate gut microbiota, and highlight the probiotic potential of milk S. salivarius and S. parasanguinis strains.
Serum Uric Acid Levels at Admission Could Predict the Chronic Post-stroke Fatigue
Authors: Ren Wenwei , Wu Junxin , Wu Zijing , Yang Shuang , Jiang Xiaofang , Xu Minjie , Wu Beilan , Xie Caixia , He Jincai , Yu Xin
Published: February 2022

Background

Post-stroke fatigue (PSF) is a frequent complication of stroke. Serum uric acid (SUA) is frequently thought to be a risk factor for stroke. This study aimed to investigate whether SUA also played a role in PSF.

Methods

Subjects with ischemic stroke were screened from The First Affiliated Hospital of Wenzhou Medical University between January 2020 and October 2020. Patients' fatigue symptoms were assessed by the Fatigue severity scale (FSS). To investigate the relationship between SUA and PSF, binary logistic regression analysis was conducted, with the confounders being controlled. SUA levels were divided into four layers (Q1 ≤ 245 μmol/L; Q2 246–308 μmol/L; Q3 309–365 μmol/L; Q4 ≥366 μmol/L) based on the quartiles.

Results

SUA levels were significantly higher in the PSF group (345.96 ± 73.78 μmol/L) than the non-PSF group (295.97 ± 87.8 μmol/L, P < 0.001). There were no differences in any other variables between these two groups. After adjusting the confounders, the risk of PSF in the Q4 layer (≥366 μmol/L) was 6.05 times (95% CI 1.79–20.43, P = 0.004) higher than that in Q1 (≤245 μmol/L).

Conclusion

High SUA at admission was an independent risk factor for fatigue 1 year after stroke onset. High SUA (≥366 μmol/L) during stroke deserves more attention, and active control of high SUA levels may be beneficial to reduce the incidence of PSF in the chronic stage following stroke.
Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10
Authors: Cheng Jing , Li Chunyang , Ying Yingfen , Lv Jieqiang , Qu Xianqin , McGowan Eileen , Lin Yiguang , Zhu Xueqiong
Published: February 2022

Background: Endometriosis affects endometrial receptivity, a key factor for successful embryo implantation. Metformin treatment is associated with alleviating the symptoms of endometriosis; however the mechanism of metformin action is unclear. Neoangiogenesis plays an important role in the development and recurrence of endometriosis. In addition, the leukemia inhibitor factor (LIF) and HOXA10 genes are also distinguishing markers of endometriosis (decrease) and endometrial receptivity (increase). This study investigated the therapeutic potentials of metformin and the underlying mechanism using an in vivo rat endometriosis model.

Methods: Female Wistar albino mature rats with experimentally induced endometriosis were used in this study. Metformin was administered at doses of 100 mg/kg/d and 200 mg/kg/d. The volume of endometriotic implants was assessed. The protein and mRNA expression of the vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), the endometrial receptivity markers, LIF and HOXA10, were measured in the endometrium of rats with endometriosis.

Results: Metformin treatment significantly suppressed the growth of endometriotic implants. Further, the expression of VEGF and MMP-9 protein and mRNA in endometriotic implants were significantly reduced. Metformin also significantly upregulated LIF and HOXA10 expression in endometrium from rats with endometriosis. The inhibitory effect of metformin on the growth of endometriotic implants, VEGF and MMP-9, and upregulating effect on LIF and HOXA10, was optimal at a dose of 100 mg/kg/d.

Conclusion: Our in vivo data demonstrates that metformin treatment alleviates endometriosis and potentiates endometrial receptivity. The underlying mechanisms are associated with decreased expression of VEGF and MMP-9 genes and upregulation of the LIF and HOXA10 genes. The effect of metformin was optimal at 100 mg/kg/d. These findings provide a potential alternative for women with endometriosis with the potential to increase fertility. Metformin is an approved drug by FDA for diabetes and this study may add another potential clinical use for metformin.
Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis
Authors: Nong Hai-bin , Zhang Ya-nan , Bai Yi-guang , Zhang Qiong , Liu Ming-fu , Zhou Quan , Shi Zhuo-hua , Zeng Gao-feng , Zong Shao-Hui
Published: February 2022

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro.

Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis.

Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice.

Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.
Relationship Between Family Functioning and Medication Adherence in Chinese Patients With Mechanical Heart Valve Replacement: A Moderated Mediation Model
Authors: Ni Hong , Lin Yanjuan , Peng Yanchun , Li Sailan , Huang Xizhen , Chen Liangwan
Published: February 2022

Background: Medication adherence is crucial for patients with mechanical heart valve replacement. Although families functioning is positively associated with medication adherence, little is known about the underlying mechanisms.

Objective: To test whether family functioning affects medication adherence through illness perceptions and whether this mediating effect was moderated by medication literacy.

Methods: 319 patients after mechanical heart valve replacement were included in this cross-sectional study from June 2021 to October 2021. Data regarding family functioning, illness perceptions, medication adherence, and medication literacy were collected through questionnaires. The moderated mediation model was examined by Hayes’s PROCESS macro, based on the bootstrapping method.

Results: The results revealed illness perceptions partially mediated the association of family functioning on medication adherence [β = 0.08, 95% confidence intervals: (0.04, 0.12)], and this effect was stronger for patients with low medication literacy than those with high literacy [β = −0.36, 95% CI: (−0.50, −0.22)]. Furthermore, the relationship between family functioning and medication adherence was only significant in patients with low medication literacy [β= 0.36, 95% CI: (0.23, 0.50)].

Conclusion: The mediating effect of illness perceptions between family functioning and medication adherence was moderated by medication literacy. Efforts to improve medication adherence by targeting at improving family functioning may be more effective when considering illness perceptions, especially for patients with limited medication literacy.
Metabolomic Impact of Lidocaine on a Triple Negative Breast Cancer Cell Line
Authors: Chamaraux-Tran Thiên-Nga , Muller Marie , Pottecher Julien , Diemunsch Pierre A. , Tomasetto Catherine , Namer Izzie-Jacques , Dali-Youcef Nassim
Published: February 2022

Background: Metabolomics and onco-anesthesia are two emerging research fields in oncology. Metabolomics (metabolites analysis) is a new diagnostic and prognostic tool that can also be used for predicting the therapeutic or toxic responses to anticancer treatments. Onco-anesthesia studies assess the impact of anesthesia on disease-free and overall survival after cancer surgery. It has been shown that local anesthetics (LA), particularly lidocaine (LIDO), exert antitumor properties both in vitro and in vivo and may alter the biologic fingerprints of cancer cells. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line.

Methods: Breast cancer MDA-MB-231 cells were exposed for 4 h to 0.5 mM LIDO or vehicle (n = 4). The metabolomic fingerprint was characterized by high resolution magic angle spinning NMR spectroscopy (HRMAS). The multivariate technique using the Algorithm to Determine Expected Metabolite Level Alteration (ADEMA) (Cicek et al., PLoS Comput. Biol., 2013, 9, e1002859), based on mutual information to identify expected metabolite level changes with respect to a specific condition, was used to determine the metabolites variations caused by LIDO.

Results: LIDO modulates cell metabolites levels. Several pathways, including glutaminolysis, choline, phosphocholine and total choline syntheses were significantly downregulated in the LIDO group.

Discussion: This is the first study assessing the impact of LIDO on metabolomic fingerprint of breast cancer cells. Among pathways downregulated by LIDO, many metabolites are reported to be associated with adverse prognosis when present at a high titer in breast cancer patients. These results fit with the antitumor properties of LIDO and suggest its impact on metabolomics profile of cancer cells. These effects of LIDO are of clinical significance because it is widely used for local anesthesia with cutaneous infiltration during percutaneous tumor biopsy. Future in vitro and preclinical studies are necessary to assess whether metabolomics analysis requires modification of local anesthetic techniques during tumor biopsy.
Ayurveda-based Botanicals as Therapeutic Adjuvants in Paclitaxel-induced Myelosuppression
Authors: Saggam Akash , Kale Prathamesh , Shengule Sushant , Patil Dada , Gautam Manish , Tillu Girish , Joshi Kalpana , Gairola Sunil , Patwardhan Bhushan
Published: February 2022

Chemotherapy-induced myelosuppression is one of the major challenges in cancer treatment. Ayurveda-based immunomodulatory botanicalsAsparagus racemosusWilld (AR/Shatavari) andWithania somnifera(L.). Dunal (WS/Ashwagandha) have potential role to manage myelosuppression. We have developed a method to study the effects of AR and WS as therapeutic adjuvants to counter paclitaxel (PTX)-induced myelosuppression. Sixty female BALB/c mice were divided into six groups—vehicle control (VC), PTX alone, PTX with aqueous and hydroalcoholic extracts of AR (ARA, ARH) and WS (WSA, WSH). The myelosuppression was induced in mice by intraperitoneal administration of PTX at 25 mg/kg dose for three consecutive days. The extracts were orally administered with a dose of 100 mg/kg for 15 days prior to the induction with PTX administration. The mice were observed daily for morbidity parameters and were bled from retro-orbital plexus after 2 days of PTX dosing. The morbidity parameters simulate clinical adverse effects of PTX that include activity (extreme tiredness due to fatigue), behavior (numbness and weakness due to peripheral neuropathy), body posture (pain in muscles and joints), fur aspect and huddling (hair loss). The collected samples were used for blood cell count analysis and cytokine profiling using Bio-Plex assay. The PTX alone group showed a reduction in total leukocyte and neutrophil counts (4,800 ± 606; 893 ± 82) when compared with a VC group (9,183 ± 1,043; 1,612 ± 100) respectively. Pre-administration of ARA, ARH, WSA, and WSH extracts normalized leukocyte counts (10,000 ± 707; 9,166 ± 1,076; 10,333 ± 1,189; 9,066 ± 697) and neutrophil counts (1,482 ± 61; 1,251 ± 71; 1,467 ± 121; 1,219 ± 134) respectively. Additionally, higher morbidity score in PTX group (7.4 ± 0.7) was significantly restricted by ARA (4.8 ± 1.1), ARH (5.1 ± 0.6), WSA (4.5 ± 0.7), and WSH (5 ± 0.8). (Data represented in mean ± SD). The extracts also significantly modulated 20 cytokines to evade PTX-induced leukopenia, neutropenia, and morbidity. The AR and WS extracts significantly prevented PTX-induced myelosuppression (p< 0.0001) and morbidity signs (p< 0.05) by modulating associated cytokines. The results indicate AR and WS as therapeutic adjuvants in cancer management.
Terahertz Dating of Sedimentary Rocks
Authors: Meng Zhaohui , Zhan Honglei , Chen Ru , Miao Xinyang , Zhao Kun
Published: February 2022

The depositional products of sedimentary rocks provide vital references for investigating the paleoenvironment, paleogeography, and tectonic evolution history. However, the detection methods of geological evolution are still relatively complicated, and how to combine geological age and geological evolution is confusing. Based on the sensitivity of terahertz waves to organic matter, a THz dating method was introduced for characterizing the geological age of sedimentary rocks. In this study, the geological evolution of Liujiang Basin was analyzed by using terahertz time domain spectroscopy (THz-TDS). According to the close relation between organic matter content and sedimentary environment, it can be inferred that the geological deposition in this area is affected by Marine cover. In addition, the refractive index of Ordovician sedimentary rocks is significantly higher than that of other sedimentary rocks. Based on these results, it is inferred that the sedimentary environment of the Liujiang Basin gradually changed from continental deposition to deep-water marine deposition from the Neoproterozoic to the Ordovician, and the sea water gradually retreated due to the crustal movement, resulting in a transition from deep-water deposition to continental inshore ocean facies deposition. These findings are highly consistent with the geological history of the study area. Combined with principal component analysis (PCA) technology, the relative geological age of sedimentary rocks can be divided. Our study con-firmed the reliability of this THz dating technique, which provides an effective way to study the geological evolution history of sedimentary rocks.
Tuning the Consonance of Microscopic Neuro-Cardiac Interactions Allows the Heart Beats to Play Countless Genres
Authors: Franzoso Mauro , Dokshokova Lolita , Vitiello Libero , Zaglia Tania , Mongillo Marco
Published: February 2022

Different from skeletal muscle, the heart autonomously generates rhythmic contraction independently from neuronal inputs. However, speed and strength of the heartbeats are continuously modulated by environmental, physical or emotional inputs, delivered by cardiac innervating sympathetic neurons, which tune cardiomyocyte (CM) function, through activation of β-adrenoceptors (β-ARs). Given the centrality of such mechanism in heart regulation, β-AR signaling has been subject of intense research, which has reconciled the molecular details of the transduction pathway and the fine architecture of cAMP signaling in subcellular nanodomains, with its final effects on CM function. The importance of mechanisms keeping the elements of β-AR/cAMP signaling in good order emerges in pathology, when the loss of proper organization of the transduction pathway leads to detuned β-AR/cAMP signaling, with detrimental consequences on CM function. Despite the compelling advancements in decoding cardiac β-AR/cAMP signaling, most discoveries on the subject were obtained in isolated cells, somehow neglecting that complexity may encompass the means in which receptors are activated in the intact heart. Here, we outline a set of data indicating that, in the context of the whole myocardium, the heart orchestra (CMs) is directed by a closely interacting and continuously attentive conductor, represented by SNs. After a roundup of literature on CM cAMP regulation, we focus on the unexpected complexity and roles of cardiac sympathetic innervation, and present the recently discovered Neuro-Cardiac Junction, as the election site of “SN-CM” interaction. We further discuss how neuro-cardiac communication is based on the combination of extra- and intra-cellular signaling micro/nano-domains, implicating neuronal neurotransmitter exocytosis, β-ARs and elements of cAMP homeostasis in CMs, and speculate on how their dysregulation may reflect on dysfunctional neurogenic control of the heart in pathology.
Selection and Validation of Reference Genes for Quantitative Real-Time PCR Normalization in Athetis dissimilis (Lepidoptera: Noctuidae) Under Different Conditions
Authors: Tang Jinrong , Liang Gemei , Dong Shaoqi , Shan Shuang , Zhao Man , Guo Xianru
Published: February 2022

Reference genes are the key to study gene expression patterns using quantitative real-time PCR (qRT-PCR). No studies on the reference genes of Athetis dissimilis, an important agricultural pest, have been reported. In order to determine the reference genes for qRT-PCR normalization in A. dissimilis under different conditions, 10 candidate genes [18S ribosomal protein (18S), 28S ribosomal protein (28S), arginine kinase (AK), elongation factor 1 alpha (EF1-α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein L32 (RPL32), ribosomal protein L40 (RPL40), alpha-tubulin (α-TUB), beta-actin (β-ACT), and beta-tubulin (β-TUB)] of A. dissimilis were selected to evaluate their stability as reference genes under different biotic and abiotic conditions by using five tools, geNorm, NormFinder, BestKeeper, ΔCt, and RefFinder. Furthermore, CSP1 and superoxide dismutase (SOD) were used as target genes to validate the candidate reference genes. The results showed that different reference genes were needed under different experimental conditions, among which, EF-1α, RPL40, and 18S are most suitable reference genes for studying genes related development stages of A. dissimilis, RPL40 and α-TUB for larval tissues, α-TUB and 28S for adult tissues, EF-1α and β-ACT for insecticidal treatments, β-ACT and 28S for temperature treatments, EF-1α and β-ACT for starvation treatments, RPL40 and 18S for dietary treatments, and 18S, 28S, and α-TUB for all the samples. These results provide suitable reference genes for studying gene expression in A. dissimilis under different experimental conditions, and also lay the foundation for further research into the function of related genes in A. dissimilis.
Benefits and Limitations to Plastic Mulching and Nitrogen Fertilization on Grain Yield and Sulfur Nutrition: Multi-Site Field Trials in the Semiarid Area of China
Authors: Luo Laichao , Hui Xiaoli , He Gang , Wang Sen , Wang Zhaohui , Siddique Kadambot H. M.
Published: February 2022

Plastic mulching (PM) is widely used to improve crop water use efficiency and grain yield, but few studies have reported the effects of PM on cereal crop quality, especially sulfur (S) nutrition of wheat, which has significant effects on grain protein content, dough rheology, baking quality and human health. To fill this knowledge gap, we conducted a multi-site field experiment on the Loess Plateau from 2014 to 2016 to study the effects of PM combined with nitrogen (N) fertilizer on grain yield, shoot S accumulation, and grain S concentration of winter wheat in dryland. Compared with no mulching (NM), PM increased grain yield by 13.7% but decreased grain S concentration, S requirement for 1,000 kg–1 grain, soil available S concentration, and post-anthesis S uptake by 9.0, 9.7, 24.4, and 51.8%, respectively. Plastic mulching significantly increased shoot S accumulation at anthesis by 19.2%, but there was no significant difference at maturity. Additionally, grain S concentration and S requirement had a linear-plateau relationship with N fertilization amount, reaching maximum values at 110 and 127 kg N ha–1 under PM, 37.5 and 27.0% higher than those under NM. Furthermore, shoot S accumulation and N application rates well-fitted the linear-plateau model at anthesis and maturity. At maturity, straw, grain, and shoots accumulated the most S at threshold N rates of 120, 85 and 110 kg N ha–1, respectively. Crucially, stem + leaf S concentration at anthesis had a significant linear relationship with grain S concentration under PM; a 1 g kg–1 increase in stem leaf concentration corresponded with a 0.24 g kg–1 increase in grain S concentration. This study’s findings suggest that combining soil S supplementation with optimal N fertilizer under PM in northwest China and other regions with similar cropping systems increases grain S concentration and improves nutritional and processing qualities.
Characterization of Repetitive DNA in Saccharum officinarum and Saccharum spontaneum by Genome Sequencing and Cytological Assays
Authors: Wang Kai , Xiang Dong , Xia Kai , Sun Bo , Khurshid Haris , Esh Ayman M. H. , Zhang Hui
Published: February 2022

In most plant species, DNA repeated elements such as satellites and retrotransposons are composing the majority of their genomes. Saccharum officinarum (2n = 8x = 80) and S. spontaneum (2n = 40–128) are the two fundamental donors of modern sugarcane cultivars. These two species are polyploids with large genome sizes and are enriched in repetitive elements. In this work, we adopted a de novo strategy to isolate highly repetitive and abundant sequences in S. officinarum LA Purple and S. spontaneum SES208. The findings obtained from alignment to the genome assemblies revealed that the vast majority of the repeats (97.9% in LA Purple and 96.5% in SES208) were dispersed in the respective genomes. Fluorescence in situ hybridization assays were performed on 27 representative repeats to investigate their distributions and abundances. The results showed that the copies of some highly repeated sequences, including rDNA and centromeric or telomeric repeats, were underestimated in current genome assemblies. The analysis of the raw read mapping strategy showed more copy numbers for all studied repeats, suggesting that copy number underestimation is common for highly repeated sequences in current genome assemblies of LA Purple and SES208. In addition, the data showed that the centromeric retrotransposons in all SES208 centromeres were absent in certain S. spontaneum clones with different ploidies. This rapid turnover of centromeric DNA in sugarcane provides new clues regarding the pattern of centromeric retrotransposon formation and accumulation.
Neighborhood Effects on Tree Mortality Depend on Life Stage of Neighbors
Authors: He Yi , Liu Heming , Yang Qingsong , Cao Ye , Yin Huimin , Zhou Zhengkang , Yu Qiuwu , Wang Xihua
Published: February 2022

Neighborhood effects are a crucial ecological processes that allow species to coexist in a forest. Conspecific and heterospecific neighbors, as major group classifications, affect tree mortality through various mechanisms associated with neighbor life stages. However, the influence of neighbor life stages on neighborhood effects and by what mechanisms remains a knowledge gap. Here we censused the mortality of 82,202 trees belonging to 30 species in a 20-ha subtropical forest and classified their neighbors into the following life stages: earlier, same and later. Next, we implemented generalized linear mixed models to estimate the effect of neighbors at different life stages on tree mortality. Our results showed that conspecific later stage neighbors had a positive effect on tree mortality overall, while conspecific earlier stage neighbors had a negative effect on tree mortality. Furthermore, these opposing effects appear to offset each other so that the overall effect of conspecific neighbors on tree mortality is weakened. In contrast, heterospecific neighbors had a decreasing effect on tree mortality overall. These effects are consistent with those of later stage heterospecific neighbors. Our findings demonstrate that neighbors strongly impact tree mortality, and their specific effects are closely related to neighbor life stages. Further, any single effect from one neighbor life stage may disturb or dominate the total effects of the neighbors. Therefore, the neighbors must be divided into different life stages to best explain the neighborhood effect on forest dynamics.