Miracle-dz/UniFAR-FTUs huggingface dataset:
The Anti-Inflammatory and Antimicrobial Potential of Selected Ethnomedicinal Plants from Sri Lanka

Traditional folk medicine in Sri Lanka is mostly based on plants and plant-derived products, however, many of these medicinal plant species are scientifically unexplored. Here, we evaluated the anti-inflammatory and antimicrobial potency of 28 different extracts prepared from seven popular medicinal plant species employed in Sri Lanka. The extracts were subjected to cell-based and cell-free assays of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1, and nitric oxide (NO) scavenging activity. Moreover, antibacterial and disinfectant activities were assessed. Characterization of secondary metabolites was achieved by gas chromatography coupled to mass spectrometric (GC-MS) analysis. n-Hexane- and dichloromethane-based extracts of Garcinia cambogia efficiently suppressed 5-LO activity in human neutrophils (IC50 = 0.92 and 1.39 µg/mL), and potently inhibited isolated human 5-LO (IC50 = 0.15 and 0.16 µg/mL) and mPGES-1 (IC50 = 0.29 and 0.49 µg/mL). Lipophilic extracts of Pothos scandens displayed potent inhibition of mPGES-1 only. A methanolic extract of Ophiorrhiza mungos caused significant NO scavenging activity. The lipophilic extracts of G. cambogia exhibited prominent antibacterial and disinfectant activities, and GC-MS analysis revealed the presence of fatty acids, sesquiterpenes and other types of secondary metabolites. Together, our results suggest the prospective utilization of G. cambogia as disinfective agent with potent anti-inflammatory properties.
PF74 and Its Novel Derivatives Stabilize Hexameric Lattice of HIV-1 Mature-Like Particles

A major structural retroviral protein, capsid protein (CA), is able to oligomerize into two different hexameric lattices, which makes this protein a key component for both the early and late stages of HIV-1 replication. During the late stage, the CA protein, as part of the Gag polyprotein precursor, facilitates protein–protein interactions that lead to the assembly of immature particles. Following protease activation and Gag polyprotein processing, CA also drives the assembly of the mature viral core. In the early stage of infection, the role of the CA protein is distinct. It controls the disassembly of the mature CA hexameric lattice i.e., uncoating, which is critical for the reverse transcription of the single-stranded RNA genome into double stranded DNA. These properties make CA a very attractive target for small molecule functioning as inhibitors of HIV-1 particle assembly and/or disassembly. Of these, inhibitors containing the PF74 scaffold have been extensively studied. In this study, we reported a series of modifications of the PF74 molecule and its characterization through a combination of biochemical and structural approaches. Our data supported the hypothesis that PF74 stabilizes the mature HIV-1 CA hexameric lattice. We identified derivatives with a higher in vitro stabilization activity in comparison to the original PF74 molecule.
Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway.

BACKGROUND Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. OBJECTIVE To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. METHODS Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. RESULTS We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal‑regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. CONCLUSION Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.
Knockdown of UTX/KDM6A Enriches Precursor Cell Populations in Urothelial Cell Cultures and Cell Lines

The histone demethylase UTX (gene: KDM6A) directs cell and tissue differentiation during development. Deleterious mutations in KDM6A occur in many human cancers, most frequently in urothelial carcinoma. The consequences of these mutations are poorly understood; plausibly, they may disturb urothelial differentiation. We therefore investigated the effects of UTX siRNA-mediated knockdown in two in vitro models of urothelial differentiation; namely, primary cultures of urothelial epithelial cells treated with troglitazone and PD153035 and the immortalized urothelial cell line HBLAK treated with high calcium and serum. In both models, efficient UTX knockdown did not block morphological and biochemical differentiation. An apparent delay was due to a cytotoxic effect on the cell cultures before the initiation of differentiation, which induced apoptosis partly in a p53-dependent manner. As a consequence, slowly cycling, smaller, KRT14high precursor cells in the HBLAK cell line were enriched at the expense of more differentiated, larger, proliferating KRT14low cells. UTX knockdown induced apoptosis and enriched KRT14high cells in the BFTC-905 papillary urothelial carcinoma cell line as well. Our findings suggest an explanation for the frequent occurrence of KDM6A mutations across all stages and molecular subtypes of urothelial carcinoma, whereby loss of UTX function does not primarily impede later stages of urothelial differentiation, but favors the expansion of precursor populations to provide a reservoir of potential tumor-initiating cells.
Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of Elovl6 on Lipid and Glucose Metabolism in Zebrafish

Elongation of very long-chain fatty acids protein 6 (Elovl6) has been reported to be associated with clinical treatments of a variety of metabolic diseases. However, there is no systematic and comprehensive study to reveal the regulatory role of Elovl6 in mRNA, protein and phosphorylation levels. We established the first knock-out (KO), elovl6−/−, in zebrafish. Compared with wild type (WT) zebrafish, KO presented significant higher whole-body lipid content and lower content of fasting blood glucose. We utilized RNA-Seq, tandem mass tag (TMT) labeling-based quantitative technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform the transcriptomic, proteomic and phosphoproteomic analyses of livers from WT and elovl6−/− zebrafish. There were 734 differentially expressed genes (DEG) and 559 differentially expressed proteins (DEP) between elovl6−/− and WT zebrafish, identified out of quantifiable 47251 transcripts and 5525 proteins. Meanwhile, 680 differentially expressed phosphoproteins (DEPP) with 1054 sites were found out of quantifiable 1230 proteins with 3604 sites. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of the transcriptomic and proteomic data further suggested that the abnormal lipid metabolism and glucose metabolism in KO were mainly related to fatty acid degradation and biosynthesis, glycolysis/gluconeogenesis and PPAR signaling pathway. Based on phosphoproteomic analyses, some kinases critical for lipid metabolism and glucose metabolism, including ribosomal protein S6 kinase (Rps6kb), mitogen-activated protein kinase14 (Mapk14) and V-akt murine thymoma viral oncogene homolog 2-like (Akt2l), were identified. These results allowed us to catch on the regulatory networks of elovl6 on lipid and glucose metabolism in zebrafish. To our knowledge, this is the first multi-omic study of zebrafish lacking elovl6, which provides strong datasets to better understand many lipid/glucose metabolic risks posed to human health.
Preconception diet, fertility, and later health in pregnancy.

PURPOSE OF REVIEW Women should enter pregnancy in the best possible health. There is increasing recognition of the importance of nutrition for reproductive health; however, key dietary factors in relation to optimizing fertility are nonexistent. The purpose of this review is to investigate dietary factors, preconception, and the association with fertility and later health in pregnancy. RECENT FINDINGS This article summarizes recent literature assessing preconception dietary intake and the association with fertility, time to pregnancy, and also the relationship with polycystic ovary syndrome and gestational diabetes; these conditions associate with each other, and also with infertility. The impact of paternal diet is also reported. SUMMARY There is recent interest investigating diet and time to pregnancy, suggesting higher intakes of fruit, minimal intake of fast food and sugar sweetened beverages, and a diet lower in glycemic load, may improve time to pregnancy. There is minimal recent literature on paternal diet and impact on fertility. Present advice to women with polycystic ovary syndrome is in line with international recommendations for lifestyle management to improve reproductive outcomes; and for gestational diabetes, prepregnancy may be an optimal time to improve dietary intakes, particularly through consumption of an overall healthy dietary pattern or a Mediterranean-style dietary pattern.
Serum Omentin Levels in Patients with Prostate Cancer and Associations with Sex Steroids and Metabolic Syndrome

Mechanisms linking obesity and prostate cancer (PC) include increased insulin signaling, persistent inflammation, and altered adipocytokines secretion. Previous studies indicated that omentin may play a potential role in cancerogenesis of different sites, including the prostate. In this study, we focused on the hormonal and metabolic characteristics of men recruited for prostate biopsy. We evaluated serum concentrations of adipocytokines and sex steroids where concentrations are related to the adiposity: omentin, leptin, testosterone, estradiol, and sex hormone-binding globulin (SHBG). Aim: The aim of the study was to assess the concentration of serum omentin in men with PC. We also investigated relationships between omentin, leptin, sex steroids, SHBG, age, and metabolic syndrome (MS). Methods: Our study was conducted on 72 patients with PC and 65 men with benign prostate hyperplasia (BPH). Both groups were compared for body mass index. Results: Comparing men with PC to subjects with BPH there were significantly higher serum concentrations of omentin, estradiol, and prostate specific antigen (PSA) in the former. Estradiol/testosterone ratio, which is a marker of testosterone to estradiol conversion, was also significantly higher in the PC group. MS was diagnosed in 47 men with PC and in 30 men with BPH, the prevalence was significantly higher in the PC group. When the subjects with PC were subdivided into two subgroups, the serum omentin did not differ between those with MS and without MS. In the overall sample serum, omentin was positively associated with age, SHBG, and leptin. A positive correlation was also found between omentin and estradiol/testosterone ratio, and negatively with testosterone/SHBG ratio. Positive correlations were noted between age and SHBG, PSA and estradiol/testosterone ratio. In our study, a drop of total testosterone and testosterone/SHBG ratio, due to age, was also demonstrated. Conclusions: In patients with prostate cancer, serum omentin may be a diagnostic indicator. Omentin levels do not correlate with estradiol or testosterone concentrations but they are related to the testosterone/SHBG ratio. Omentin is not associated with an increased likelihood of having metabolic syndrome in men with prostate cancer.
Versatile Tool for Droplet Generation in Standard Reaction Tubes by Centrifugal Step Emulsification

We present a versatile tool for the generation of monodisperse water-in-fluorinated-oil droplets in standard reaction tubes by centrifugal step emulsification. The microfluidic cartridge is designed as an insert into a standard 2 mL reaction tube and can be processed in standard laboratory centrifuges. It allows for droplet generation and subsequent transfer for any downstream analysis or further use, does not need any specialized device, and manufacturing is simple because it consists of two parts only: A structured substrate and a sealing foil. The design of the structured substrate is compatible to injection molding to allow manufacturing at large scale. Droplets are generated in fluorinated oil and collected in the reaction tube for subsequent analysis. For sample sizes up to 100 µL with a viscosity range of 1 mPa·s–4 mPa·s, we demonstrate stable droplet generation and transfer of more than 6 × 105 monodisperse droplets (droplet diameter 66 µm ± 3 µm, CV ≤ 4%) in less than 10 min. With two application examples, a digital droplet polymerase chain reaction (ddPCR) and digital droplet loop mediated isothermal amplification (ddLAMP), we demonstrate the compatibility of the droplet production for two main amplification techniques. Both applications show a high degree of linearity (ddPCR: R2 ≥ 0.994; ddLAMP: R2 ≥ 0.998), which demonstrates that the cartridge and the droplet generation method do not compromise assay performance.
Evaluation of Inflammation Caused by Cardiopulmonary Bypass in a Small Animal Model

Extracorporeal circulation (ECC) methods are being increasingly used for mechanical support of respiratory and cardio-circulatory failure. Especially, cardiopulmonary bypass (CPB) during cardiovascular surgery, sustenance of the patient’s life by providing an appropriate blood flow and oxygen supply to principal organs. On the other hand, systemic inflammatory responses in patients undergoing cardiovascular surgery supported by CPB contribute significantly to CPB-associated mortality and morbidity. Our previous research showed that CPB causes a systemic inflammatory response and organ damage in a small animal CPB model. We have been studying the effects of hyperoxia and blood plasma substitute on CPB. In this review, we present a study focusing on the systemic inflammatory response during CPB, along with our findings.
GoPrime: Development of an In Silico Framework to Predict the Performance of Real-Time PCR Primers and Probes Using Foot-and-Mouth Disease Virus as a Model

Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result in false-negative results and errors in quantifying target sequences. Primer and probe sequences therefore require continual evaluation to ensure they remain fit for purpose. This paper describes the development of a linear model and associated computational tool (GoPrime) designed to predict the performance of rPCR primers and probes across multiple sequence data. Empirical data were generated using DNA oligonucleotides (n = 90) that systematically introduced variation in the primer and probe target regions of a diagnostic assay routinely used to detect foot-and-mouth disease virus (FMDV); an animal virus that exhibits a high degree of sequence variability. These assays revealed consistent impacts of patterns of substitutions in primer and probe-sites on rPCR cycle threshold (CT) and limit of detection (LOD). These data were used to populate GoPrime, which was subsequently used to predict rPCR results for DNA templates (n = 7) representing the natural sequence variability within FMDV. GoPrime was also applicable to other areas of the FMDV genome, with predictions for the likely targets of a FMDV-typing assay consistent with published experimental data. Although further work is required to improve these tools, including assessing the impact of primer-template mismatches in the reverse transcription step and the broader impact of mismatches for other assays, these data support the use of mathematical models for rapidly predicting the performance of rPCR primers and probes in silico.
ENDOTHELIN-1-INDUCED ENDOTHELIAL MICROVESICLES IMPAIR ENDOTHELIAL CELL FUNCTION.

The aim of this study was to determine the effects of endothelin-1 (ET-1)-generated endothelial microvesicles (EMVs) on endothelial cell inflammation, apoptosis and endothelial nitric oxide synthase (eNOS). Human umbilical vein endothelial cells (HUVECs) were treated with ET-1 for 24 h. EMVs released into the supernatant from cells treated with ET-1 or vehicle were isolated and quantified. EMV release was higher (P<0.05) in cells treated with ET-1 compared with control (95+15 vs 54+5 EMV/µL). Fresh HUVECs were then treated with either ET-1, ET-1-induced EMVs or control EMVs for 24 h. ET-1-generated EMVs induced significantly higher release of interleukin (IL)-6 (181.0±16.0 vs 132.1±8.1 pg/mL) and IL-8 (303.4±37.4 vs 211.8+10.0 pg/mL) as well as greater total NF-κB p65 (76.0+7.6 vs 57.1+2.1 AU) and active NF-κB p65 (Ser536) (11.6+0.9 vs 6.8+1.0 AU) expression than control EMVs. There were no significant differences in expression of caspase-9 (230.1+24.3 vs 243.6+22.3 AU), caspase-3 (271.9+22.7 vs 265.1+30.5 AU) and active caspase-3 (4.4+0.4 vs 4.3+0.1 AU) in cells treated with ET-1-EMVs versus control EMVs. Total eNOS (108.4+11.4 vs 158.8+1.6 AU) and activated eNOS (4.7+0.5 vs 9.6+1.4 AU) were significantly lower in endothelial cells treated with ET-1-generated EMVs compared with control EMVs. The effects of ET-1-generated EMVs on cellular markers and mediators of endothelial inflammation as well as eNOS function was comparable to the effects of ET-1. In summary, ET-1 induces an EMV phenotype that adversely affects endothelial cell function. ET-1-generated EMVs may contribute to the atherogenic effect of ET-1.
Outcome Analysis of the Effects of Helmet Therapy in Infants with Brachycephaly

Brachycephaly has several potential deleterious effects, including malocclusion, sleep apnea, and abnormal posture. Nevertheless, the research regarding helmet therapy as a treatment strategy for brachycephaly is limited. Herein, we aimed to analyze the factors influencing the effects of helmet therapy in infants with brachycephaly. We retrospectively reviewed the records of 207 infants aged 3–14 months with a cranial index (CI) >90% who received helmet therapy between May 2016 and October 2019 and complied with the treatment protocol well. We used a multiple regression analysis to determine which factors affected the duration of therapy and a Jonckheere–Terpstra test to establish differences in the duration of helmet therapy according to age and severity. We identified brachycephaly severity (p < 0.001), asymmetry (p < 0.001), and age (p < 0.001) as factors affecting the duration of therapy. Helmet therapy might be effective for infants with moderate to severe brachycephaly, assuming good protocol compliance. In addition, younger treatment initiation age and less severe and less asymmetric brachycephaly significantly shorten the treatment duration.
Unraveling Heterogeneity of Coral Microbiome Assemblages in Tropical and Subtropical Corals in the South China Sea

Understanding the coral microbiome is critical for predicting the fidelity of coral symbiosis with growing surface seawater temperature (SST). However, how the coral microbiome will respond to increasing SST is still understudied. Here, we compared the coral microbiome assemblages among 73 samples across six typical South China Sea coral species in two thermal regimes. The results revealed that the composition of microbiome varied across both coral species and thermal regimes, except for Porites lutea. The tropical coral microbiome displayed stronger heterogeneity and had a more un-compacted ecological network than subtropical coral microbiome. The coral microbiome was more strongly determined by environmental factors than host specificity. γ- (32%) and α-proteobacteria (19%), Bacteroidetes (14%), Firmicutes (14%), Actinobacteria (6%) and Cyanobacteria (2%) dominated the coral microbiome. Additionally, bacteria inferred to play potential roles in host nutrients metabolism, several keystone bacteria detected in human and plant rhizospheric microbiome were retrieved in explored corals. This study not only disentangles how different host taxa and microbiome interact and how such an interaction is affected by thermal regimes, but also identifies previously unrecognized keystone bacteria in corals, and also infers the community structure of coral microbiome will be changed from a compacted to an un-compacted network under elevated SST.
Increasing Incidence of Liposarcoma: A Population-Based Study of National Surveillance Databases, 2001–2016

Rare cancers, affecting 1 in 5 cancer patients, disproportionally contribute to cancer mortality. This research focuses on liposarcoma, an understudied rare cancer with unknown risk factors and limited treatment options. Liposarcoma incident cases were identified from the U.S. Surveillance, Epidemiology, and End Result (SEER) program and the combined SEER-National Program of Cancer Registries (CNPCR) between 2001–2016. Incidence rates (age-adjusted and age-specific), 5-year survival, and the time trends were determined using SEER*stat software. Three-dimensional visualization of age–time curves was conducted for males and females. SEER liposarcoma cases represented ~30% (n = 11,162) of the nationwide pool (N = 37,499). Both sources of data showed males accounting for ~60% of the cases; 82%–86% cases were identified among whites. Age-adjusted incidence was greater among males vs. females and whites vs. blacks, whereas survival did not differ by sex and race. The dedifferentiated (57.2%), pleomorphic (64.1%), and retroperitoneal (63.9%) tumors had the worse survival. Nationwide, liposarcoma rates increased by 19%, with the annual percent increase (APC) of 1.43% (95% confidence interval (CI): 1.12–1.74). The APC was greater for males vs. females (1.67% vs. 0.89%) and retroperitoneal vs. extremity tumors (1.94% vs. 0.58%). Thus, incidence increased faster in the high-risk subgroup (males), and for retroperitoneal tumors, the low-survival subtype. The SEER generally over-estimated the rates and time trends compared to nationwide data but under-estimated time trends for retroperitoneal tumors. The time trends suggest an interaction between genetic and non-genetic modifiable risk factors may play a role in the etiology of this malignancy. Differences between SEER and CNCPR findings emphasize the need for nationwide cancer surveillance.