An Association Rule Analysis of the Acupressure Effect on Sleep Quality

Background. Sleep is recognized as an all-important physiological process, which also contributes to maintaining several bodily functions and systems. According to the Pittsburgh Sleep Quality Index (PSQI), also known as the most widely used tool in the field of subjective assessment of self-perceived sleep quality, a combination of acupoints could be more effective than single acupoint treatment in improving sleep quality. Methods. The present study was based on the extracted eligible studies rooted in a previous meta-analysis that worked on the basis of association rule mining and examined the potential kernel acupoint combinations for improving sleep quality. Results. Depending on the Apriori algorithm, we summarized 26 acupoints as binary data from the 32 eligible studies based on a previous meta-analysis and analyzed them. The top 10 most frequently selected acupoints were HT7, SP6, PC6, KI1, GV20, EM5, EX-HN3, EX-HN16, KI3, and MA-TF1. Furthermore, as deduced from 21 association rules, the primary relevant rules in the combination of acupoints are (EX-HN3, EX-HN16)=>(GV20) and (HT7, KI1)=>(PC6). Conclusions. In order to use acupuncture to improve sleep quality, integrating (EX-HN3, EX-HN16, GV20) with (HT7, KI1, PC6) acupoints could be deemed as the kernel acupoint combination.

Delayed Protein Changes During Seed Germination

Over the past decade, ample transcriptome data have been generated at different stages during seed germination; however, far less is known about protein synthesis during this important physiological process. Generally, the correlation between transcript levels and protein abundance is low, which strongly limits the use of transcriptome data to accurately estimate protein expression. Polysomal profiling has emerged as a tool to identify mRNAs that are actively translated. The association of the mRNA to the polysome, also referred to as translatome, provides a proxy for mRNA translation. In this study, the correlation between the changes in total mRNA, polysome-associated mRNA, and protein levels across seed germination was investigated. The direct correlation between polysomal mRNA and protein abundance at a single time-point during seed germination is low. However, once the polysomal mRNA of a time-point is compared to the proteome of the next time-point, the correlation is much higher. 35% of the investigated proteome has delayed changes at the protein level. Genes have been classified based on their delayed protein changes, and specific motifs in these genes have been identified. Moreover, mRNA and protein stability and mRNA length have been found as important predictors for changes in protein abundance. In conclusion, polysome association and/or dissociation predicts future changes in protein abundance in germinating seeds.

Structural insights into the modulation of PDGF/PDGFR-β complexation by hyaluronan derivatives

Angiogenesis is an important physiological process playing a crucial role in wound healing and cancer progression. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are key players in angiogenesis. Based on previous findings regarding the modulation of VEGF activity by glycosaminoglycans (GAG), here we explore the interaction of hyaluronan (HA)-based GAG with PDGF and its receptor PDGFR-β by applying molecular modeling and dynamics simulations in combination with surface plasmon resonance (SPR). Computational analysis on the interaction of oligo-hyaluronan derivatives with different sulfation pattern and functionalization shows that these GAG interact with PDGF in relevant regions for receptor recognition, and that high sulfation as well as modification with the TAMRA group convey stronger binding. On the other hand, the studied oligo-hyaluronan derivatives are predicted to scarcely recognize PDGFR-β. SPR results are in line with the computational predictions regarding the binding pattern of HA tetrasaccharide (HA4) derivatives to PDGF and PDGFR-β. Furthermore, our experimental results also show that the complexation of PDGF to PDGFR-β can be modulated by HA4 derivatives. The results found open the path for considering HA4 derivatives as potential candidates to be exploited for modulation of the PDGF/PDGFR-β signaling system in angiogenesis and related disease conditions.

Prion-Like Proteins in Phase Separation and Their Link to Disease

Aberrant protein folding underpins many neurodegenerative diseases as well as certain myopathies and cancers. Protein misfolding can be driven by the presence of distinctive prion and prion-like regions within certain proteins. These prion and prion-like regions have also been found to drive liquid-liquid phase separation. Liquid-liquid phase separation is thought to be an important physiological process, but one that is prone to malfunction. Thus, aberrant liquid-to-solid phase transitions may drive protein aggregation and fibrillization, which could give rise to pathological inclusions. Here, we review prions and prion-like proteins, their roles in phase separation and disease, as well as potential therapeutic approaches to counter aberrant phase transitions.

Autophagy Modulation and Synergistic Therapy to Combat Multidrug Resistance Breast Cancer Using Hybrid Cell Membrane Nanoparticles

The development of multidrug resistance (MDR) is a commonly observed phenomenon in many cancer types. It contributed significantly to the poor outcome of many currently available chemotherapies. Considering autophagy as one of the most important physiological process in cancer progression, we thereby proposed an anti-autophagy siRNA and doxorubicin (Dox) co-delivery system (MC/D-siR) to combat MDR breast cancer using sequential construction. Our results demonstrated the potential of MC/D-siR to effectively transfect the loaded siRNA to result in significant downregulation of intracellular autophagy level in MCF-7/Adr (Dox resistance MCF-7 cell line) cells, which in turn cut off the ATP supply and to reverse the MDR and potentiated accumulated drug retention in cells. As a result, MC/D-siR showed much elevated anticancer benefits than single loaded platforms (MC/Dox or MC/siRNA), indicating the ability for effective MDR cancer treatment through the combination of autophagy regulation and chemotherapy.

In Silico Identification of the Potential Natural Inhibitors of SARS-CoV-2 Guanine-N7 Methyltransferase.

The outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 has triggered intense scientific research into the possible therapeutic strategies that can combat the ravaging disease. One of such strategies is the inhibition of an important enzyme that affects an important physiological process of the virus. The enzyme, Guanine 7 Methyltransferase is responsible for the capping of the SARS-CoV-2 mRNA to conceal it from the host’s cellular defense. The study aims at computationally identifying the potential natural inhibitors of the SARS-CoV-2 GuanineN7 methyltransferase binding at the active site (Pocket 41). A library of small molecules was obtained from edible African plants and were molecularly docked against the SARS-CoV-2 Guanine-N7 methyltransferase (QHD43415_13. pdb) using the Pyrx software. Sinefungin, an approved antiviral drug which had a binding score of -7.6 kcal/ mol with the target was chosen as a standard. Using the molecular descriptors of the compounds, a virtual screening for oral availability was performed using the Pubchem and SWISSADME web tools. The online servers PKCSM and Molinspiration were used for further screening for pharmacokinetic properties and bioactivity respectively. The molecular dynamic simulation and analyses of the Apo and Holo proteins was performed using the GROMACS software on the Galaxy webserver. The lead compounds are Crinamidine, Marmesin and Sinensetin which are obtained from waterleaf, mango, and orange plants respectively. All the lead compounds performed better than the standard. Crinamidine is predicted to show the greatest inhibitory activity. Further tests are required to further investigate the inhibitory activities of the lead compounds.

In Silico Identification of the Potential Natural Inhibitors of SARS-CoV-2 Guanine-N7 Methyltransferase.

The outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 has triggered intense scientific research into the possible therapeutic strategies that can combat the ravaging disease. One of such strategies is the inhibition of an important enzyme that affects an important physiological process of the virus. The enzyme, Guanine 7 Methyltransferase is responsible for the capping of the SARS-CoV-2 mRNA to conceal it from the host’s cellular defense. The study aims at computationally identifying the potential natural inhibitors of the SARS-CoV-2 GuanineN7 methyltransferase binding at the active site (Pocket 41). A library of small molecules was obtained from edible African plants and were molecularly docked against the SARS-CoV-2 Guanine-N7 methyltransferase (QHD43415_13. pdb) using the Pyrx software. Sinefungin, an approved antiviral drug which had a binding score of -7.6 kcal/ mol with the target was chosen as a standard. Using the molecular descriptors of the compounds, a virtual screening for oral availability was performed using the Pubchem and SWISSADME web tools. The online servers PKCSM and Molinspiration were used for further screening for pharmacokinetic properties and bioactivity respectively. The molecular dynamic simulation and analyses of the Apo and Holo proteins was performed using the GROMACS software on the Galaxy webserver. The lead compounds are Crinamidine, Marmesin and Sinensetin which are obtained from waterleaf, mango, and orange plants respectively. All the lead compounds performed better than the standard. Crinamidine is predicted to show the greatest inhibitory activity. Further tests are required to further investigate the inhibitory activities of the lead compounds.

Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy

Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Krüppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to theCORINpromoter and enhances the promoter activity. Disruption of theKLF17gene in the endometrial cells abolishesCORINexpression. In mice,Klf17is up-regulated in the pregnant uterus.Klf17deficiency prevents uterineCorinexpression in pregnancy. Moreover,Klf17-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulatingCorinexpression and uterine physiology in pregnancy.

Oral cavity-derived exosomes as promising tool in chronic wound healing

Wound healing is an important physiological process aimed at maintaining the integrity of the skin after injury, accidentally or intentionally. Physiological wound healing involves three consecutive but overlapping phases, including hemostasis, proliferation and remodeling. Wound healing abnormalities, such as excessive wound healing (e.g. keloid) or chronic wounds (e.g. ulcers) impair normal physiological function. Many experimental studies have provided insight into wound healing. There are numerous methods that support wound healing, including popular hydrogels, vegetable oils, ultrasound and even treatment with maggots. Stem cell therapies are also very popular, but they are not safe in all cases due to having specific antibodies. In the following article, in addition to a brief overview of current healing therapies we will examine exosomal therapy, which, although new, seems to be very promising if only because of the high safety of use.Running title: Exosomes in wound healing

Landscape of RNA editing reveals new insights into the dynamic gene regulation of spermatogenesis based on integrated RNA-Seq

ABSTRACTSpermatogenesis is an important physiological process associated with male infertility. But whether there are RNA editings (REs) and what’s the role of REs during the process are still unclear. In this study, we integrated published RNA-Seq datasets and established a landscape of REs during the development of mouse spermatogenesis. 7530 editing sites among all types of male germ cells were found, which enrich on some regions of chromosome, including chromosome 17 and both ends of chromosome Y. Totally, REs occur in 2012 genes during spermatogenesis, more than half of which harbor at two different sites of the same gene at least. We also found REs mainly occur in introns, coding regions (CDSs) and intergenic regions. Moreover, about half of the REs in CDSs can cause amino acids changes. Finally, based on our adult male Kunming mice, we verified that there is a non-synonymous A-to-I RNA editing site inCog3during spermatogenesis, which is conserved not only between species but also across tissues. In short, based on the power of integrating RNA-Seq datasets, we provided the landscape of REs and found their dynamic changes during mouse spermatogenesis. This research strategy is general for other types of sequencing datasets and biological problems.