Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and modulation of inflammatory genes. The activity of nuclear receptors is key in maintaining metabolic flexibility. Their activity depends on the availability of endogenous ligands, like fatty acids or oxysterols, and their derivatives produced by the catabolic action of metabolic lipases, most of which are under the control of nuclear receptors. For example, adipose triglyceride lipase (ATGL) is activated by peroxisome proliferator-activated receptor γ (PPARγ) and conversely releases fatty acids as ligands for PPARα, therefore, demonstrating the interdependency of nuclear receptors and lipases. The diverse biological functions and importance of nuclear receptors in metabolic syndrome and NAFLD has led to substantial effort to target them therapeutically. This review summarizes recent findings on the roles of lipases and selected nuclear receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD.
Phenolic Compounds of Reynoutria sp. as Modulators of Oral Cavity Lactoperoxidase System

Lactoperoxidase (LPO) together with its (pseudo)halogenation cycle substrates, H2O2 and thiocyanate ions oxidized to hypothiocyanite ions, form one of the main systems involved in antimicrobial defense within the oral cavity. In bacterial diseases such as dental caries, lactoperoxidase is oxidized to a form known as Compound II, which is characterized by its inability to oxidize SCN–, resulting in a decreased generation of antimicrobial products. Reynoutria sp. rizome extracts, due to their high polyphenol content, have been tested as a source of compounds able to regenerate the antimicrobial activity of lactoperoxidase through converting the Compound II to the native LPO state. In the presented study, acetone extracts of R. japonica, R. sachalinensis, and R. x bohemica, together with their five fractions and four selected polyphenols dominating in the studied in extracts, were tested toward lactoperoxidase reactivating potential. For this purpose, IC50, EC50, and activation percentage were determined by Ellman’s method. Furthermore, the rate constants for the conversion of Compound I–Compound II and Compound II–native-LPO in the presence of extracts, extracts fractions, and selected polyphenols were determined. Finally, the ability to enhance the antimicrobial properties of the lactoperoxidase system was tested against Streptococcus mutans. We proved that Reynoutria sp. rhizome is the source of lactoperoxidase peroxidation cycle substrates, which can act as activators and inhibitors of the antimicrobial properties of that system. The presented study shows that the reactivation of lactoperoxidase could become a potential therapeutic target in prevention and treatment support in some infectious oral diseases.
Human Brain Lipidomics: Utilities of Chloride Adducts in Flow Injection Analysis

Ceramides have been implicated in a number of disease processes. However, current means of evaluation with flow infusion analysis (FIA) have been limited primarily due to poor sensitivity within our high-resolution mass spectrometry lipidomics analytical platform. To circumvent this deficiency, we investigated the potential of chloride adducts as an alternative method to improve sensitivity with electrospray ionization. Chloride adducts of ceramides and ceramide subfamilies provided 2- to 50-fold increases in sensitivity both with analytical standards and biological samples. Chloride adducts of a number of other lipids with reactive hydroxy groups were also enhanced. For example, monogalactosyl diacylglycerols (MGDGs), extracted from frontal lobe cortical gray and subcortical white matter of cognitively intact subjects, were not detected as ammonium adducts but were readily detected as chloride adducts. Hydroxy lipids demonstrate a high level of specificity in that phosphoglycerols and phosphoinositols do not form chloride adducts. In the case of choline glycerophospholipids, the fatty acid substituents of these lipids could be monitored by MS2 of the chloride adducts. Monitoring the chloride adducts of a number of key lipids offers enhanced sensitivity and specificity with FIA. In the case of glycerophosphocholines, the chloride adducts also allow determination of fatty acid substituents. The chloride adducts of lipids possessing electrophilic hydrogens of hydroxyl groups provide significant increases in sensitivity. In the case of glycerophosphocholines, chloride attachment to the quaternary ammonium group generates a dominant anion, which provides the identities of the fatty acid substituents under MS2 conditions.
Palyno‐morphological characterization of selected allergenic taxa of family Poaceae from Islamabad‐Pakistan using microscopic techniques

Statistics around the world show an increased risk of high allergies associated with plants. The role of allergenic pollen is now well known. The most serious allergenic diseases are asthma and rhinitis, which affect 5–30% of the population of industrialized countries. This work focuses on the exploration of allergenic grass species of Islamabad, Pakistan and use microscopic techniques to correctly identify them. This study contains 11 species of grasses which showed variations in pollen morphological features. The dominant pollen shape was prolate, prolate‐spheroidal and sub oblate. The largest polar diameter was calculated for Echinochloa crus‐galli (56.00 μm) while the largest equatorial diameter was found in Cenchrus ciliaris (45.00 μm). Exine ornamentation varied from Gemmate–verrucate, Scabrate–reugulate, Verrucate–reticulate, Gemmate–Scabrate, Fine–Gemmate, Gemmate–rugulate, Gemmate–reticulate, Gemmate–scabrate, Scabrate–verrucate, and Scabrate. Maximum exine thickness was found in Eleusine indica (4.90 μm) while in C. ciliaris (1.50 μm) the minimum thickness of exine was measured. In E. crus‐galli (1.54 μm), the largest P to E value was measured and the smallest value was noticed in Setaria verticillata (0.86 μm). The study was performed with an aim to identify the allergenic plant species in Islamabad‐Pakistan using pollen morphological studies. This study provides significant information, to arrange the pollen types within their defined classes and to discuss various pollen features for developing an allergenic pollen atlas.
Gold Nanoclusters Display Low Immunogenic Effect in Microglia Cells

Gold nanoparticles hold a great promise for both clinical and preclinical applications. The major factors impeding such applications are toxicity of new nanomaterials including e.g., pro-apoptotic activities or inflammatory effects, but also their potential to accumulate in the body or inadequate absorption, distribution, metabolism and excretion (ADME) profiles. Since such adverse effects depend on the size, form and coating of nanomaterials, the search for new, less toxic nanomaterials with low tendency to accumulate is highly active domain of research. Here, we describe optical and biological properties of Au18 gold nanoclusters (NCs), small gold nanoparticles composed of 18 atoms of gold and stabilized with glutathione ligands. These nanoclusters may be suitable for in vivo applications owing to their low toxicity and biodistribution profile. Specifically, using lactate dehydrogenase (LDH) test in P19 cell line we found that Au18 NCs display low toxicity in vitro. Importantly, using primary microglial cells we showed that at low concentrations Au18 NCs display anti-inflammatory signaling on evidence of reduced interleukin 1-β (IL1-β) levels and unchanged levels of tumor necrosis factor (TNF-α) or Ym1/2. Such effect was dose dependent as higher concentrations of Au18 NCs induced expression of pro-inflammatory cytokines and suppression of anti-inflammatory cytokine Ym1/2, pointing, thus, to global inflammatory activity. Finally, we also showed that within 3 days Au18 NCs can be completely eliminated from the liver reported as the major target organ for accumulation of gold nanoparticles. These data point to a potential of gold nanoparticles for further biomedical studies.
Virulence and Antimicrobial Resistance Profiles of Salmonella enterica Serovars Isolated from Chicken at Wet Markets in Dhaka, Bangladesh

Virulent and multi drug resistant (MDR) Salmonella enterica is a foremost cause of foodborne diseases and had serious public health concern globally. The present study was undertaken to identify the pathogenicity and antimicrobial resistance (AMR) profiles of Salmonella enterica serovars recovered from chicken at wet markets in Dhaka, Bangladesh. A total of 870 cecal contents of broiler, sonali, and native chickens were collected from 29 wet markets. The overall prevalence of S. Typhimurium, S. Enteritidis, and untyped Salmonella spp. , were found to be 3.67%, 0.57%, and 1.95% respectively. All isolates were screened by polymerase chain reaction (PCR) for eight virulence genes, namely invA, agfA, IpfA, hilA, sivH, sefA, sopE, and spvC. S. Enteritidis isolates carried all virulence genes whilst S. Typhimurium isolates carried six virulence genes except sefA and spvC. A diverse phenotypic and genotypic AMR pattern was found. Harmonic descending trends of resistance patterns were observed among the broiler, sonali, and native chickens. Interestingly, virulent and MDR Salmonella enterica serovars were found in native chicken, although antimicrobials were not used in their production cycle. The research findings anticipate that virulent and MDR Salmonella enterica are roaming in the wet markets which can easily anchor to the vendor, consumers, and in the food chain.
Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice

Simple Summary Anti-cancer effects of bioactive compounds have been extensively investigated; however, the effective dosages of the bioactive compounds are too high to be obtained by oral intake. Our study aimed to assess if combined two bioactive compounds, luteolin (LUT) and indole-3-carbinol (I3C), at low dosages that LUT or I3C along has no significant effect, synergistically exerts anti-breast cancer. We confirmed that combined LUT and I3C synergistically suppressed estrogen receptor-alpha positive breast cancer in cultured cells and cells-derived xenograft mice. Our results also indicated two possible molecular pathways involving the synergistic effects of the combination of LUT and I3C. Our findings provide a practical approach to treat or prevent breast cancer by combining two bioactive compounds. Abstract The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials.
Acute pre-exercise supplementation of combined carnosine and anserine enhances initial maximal power of Wingate tests in humans.

Classic in vitro experiments (Severin's phenomenon) demonstrated that acute carnosine supplementation may potentiate muscle contractility. However, upon oral ingestion, carnosine is readily degraded in human plasma by the highly active serum carnosinase-1 (CN1). We developed a novel strategy to circumvent CN1 by pre-exercise ingestion of combined carnosine (CARN) and anserine (ANS), the methylated analog with similar biochemical properties but more resistant to CN1. First, in vitro hydrolysis was tested by adding carnosine and anserine to human plasma, alone or in combination. Secondly, 5 subjects were supplemented with 25mg/kg anserine or 25mg/kg of each anserine and carnosine to test in vivo bioavailability. Thirdly, two double-blind, placebo-controlled, crossover studies investigated the effect of pre-exercise ANS+CARN (20mg/kg BW of each) supplementation on performance during a single all-out Wingate test following 6-minute high-intensity cycling (study A) or 3 repeated Wingate tests (study B). In vitro experiments demonstrated slower degradation of anserine vs carnosine, which was further slowed by simultaneously adding carnosine. In vivo bioavailability of plasma anserine was more prominent (2.5-fold increased AUC) when ANS+CARN vs ANS was ingested. Study A showed significantly higher (+6±11%; p=0.04) power in the first 5s of the Wingate test following ANS+CARN (12.8±2.4W/kg) vs placebo (12.1±2.2W/kg). Study B demonstrated increased peak power (+3%) throughout 3 consecutive Wingate tests (ANS+CARN 10.5±0.6W/kg vs placebo 10.2±9.9W/kg). These experiments reveal a novel acute nutritional method to effectively raise plasma anserine and carnosine by high-dose combined supplementation. This approach led to improved initial cycling power, revealing a new nutritional strategy to increase exercise performance.
Retinal and Optic Disc Vascular Changes in Patients Using Long-Term Tadalafil: A Prospective Non-Randomized Matched-Pair Study

Retinal, choroidal and optic disc vascularity has never been evaluated in patients taking PDE5is long-term. The aim of our study was to evaluate the neurostructural and vascular changes after long-term use of tadalafil, using spectral domain (SD)-optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). In the present clinical trial, 27 patients who have been taking tadalafil 20 mg on alternate days (OAD) for at least 6 months (Group A) were enrolled. The matched group consisted of 27 healthy men (Group B). Both groups of patients underwent SD-OCT to study ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) and choroidal thickness and OCTA for the evaluation of superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) and radial peripapillary capillary (RPC). A reduction in SCP, DCP and RPC vessel density was found in patients using tadalafil long-term. Retinal and optic disc toxicity may be detected using modifications of capillary vessel density. Further studies are needed to investigate the possibility of a causal association.
The Health and Development of Young Children Who Witnessed Their Parent’s Arrest Prior to Parental Jail Incarceration

Most U.S. incarceration occurs in jails, with more than 10 million annual admissions, and most individuals in jail are parents of minor children. In this short-term longitudinal study, we examined the health and development of young children who did or did not witness their parent’s arrest prior to parental jail incarceration. 228 individuals in 76 triads (incarcerated parents, children, at-home caregivers) were enrolled from four jails in two states. Jailed parents and caregivers reported on whether the child witnessed the parent’s arrest or crime. Children’s caregivers completed questionnaires about children’s emotional symptoms during the prior 6 months and demographics, as well as children’s emotional reactions to separation from the parent and child health at the initial assessment and 2 weeks later. Trained researchers conducted a developmental assessment with children while waiting to visit parents. Results of regression-based moderated mediation analyses indicated that when their emotional symptoms were high, children who witnessed parental arrest were more likely to have poorer health initially and more intense negative reactions to the parent leaving for jail. In addition, when children’s general emotional symptoms were low, children who witnessed their parent’s arrest were more likely to exhibit developmental delays, especially in their early academic skills, compared to children who did not witness the arrest. Witnessing the parent’s crime related to missed milestones in social and adaptive development. Findings have implications for policies regarding safeguarding children during parental arrest and referrals for health- and development-promotion services following parental criminal justice system involvement.
miR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review

Multiple sclerosis (MS) is a chronic, immune-mediated disease and the leading cause of disability among young adults. MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. Of them, miR-155 is a crucial regulator of inflammation and plays a role in modulating the autoimmune response in MS. miR-155 is involved in blood–brain barrier (BBB) disruption via down-regulation of key junctional proteins under inflammatory conditions. It drives demyelination processes by contributing to, e.g., microglial activation, polarization of astrocytes, and down-regulation of CD47 protein and affecting crucial transcription factors. miR-155 has a huge impact on the development of neuropathic pain and indirectly influences a regulatory T (Treg) cell differentiation involved in the alleviation of pain hypersensitivity. This review also focused on neuropsychiatric symptoms appearing as a result of disease-associated stressors, brain atrophy, and pro-inflammatory factors. Recent studies revealed the role of miR-155 in regulating anxiety, stress, inflammation in the hippocampus, and treatment-resistant depression. Inhibition of miR-155 expression was demonstrated to be effective in preventing processes involved in the pathophysiology of MS. This review aimed to support the better understanding the great role of miR-155 dysregulation in various aspects of MS pathophysiology and highlight future perspectives for this molecule.
Dietary Patterns Derived from UK Supermarket Transaction Data with Nutrient and Socioeconomic Profiles

Poor diet is a leading cause of death in the United Kingdom (UK) and around the world. Methods to collect quality dietary information at scale for population research are time consuming, expensive and biased. Novel data sources offer potential to overcome these challenges and better understand population dietary patterns. In this research we will use 12 months of supermarket sales transaction data, from 2016, for primary shoppers residing in the Yorkshire and Humber region of the UK (n = 299,260), to identify dietary patterns and profile these according to their nutrient composition and the sociodemographic characteristics of the consumer purchasing with these patterns. Results identified seven dietary purchase patterns that we named: Fruity; Meat alternatives; Carnivores; Hydrators; Afternoon tea; Beer and wine lovers; and Sweet tooth. On average the daily energy intake of loyalty card holders -who may buy as an individual or for a household- is less than the adult reference intake, but this varies according to dietary purchase pattern. In general loyalty card holders meet the recommended salt intake, do not purchase enough carbohydrates, and purchase too much fat and protein, but not enough fibre. The dietary purchase pattern containing the highest amount of fibre (as an indicator of healthiness) is bought by the least deprived customers and the pattern with lowest fibre by the most deprived. In conclusion, supermarket sales data offer significant potential for understanding population dietary patterns.
Gait speed and adverse outcomes following hospitalised exacerbation of COPD

Background The 4-m gait speed (4MGS) test is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods 213 participants hospitalised with AECOPD (52% male, mean age 72 years and mean forced expiratory volume in 1 s (FEV1) 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 year after discharge and multivariable Cox proportional hazards regressions were performed. Kaplan–Meier and competing risks analyses were conducted comparing time to all-cause readmission and mortality between 4MGS quartiles. Results 111 participants (52%) were readmitted and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797–0.945; p=0.001) per 0.1 m·s−1 increase in gait speed, and with all-cause mortality, with an adjusted subdistribution hazard ratio of 0.747 (95% CI 0.622–0.898; p=0.002) per 0.1 m·s−1 increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV1 % pred alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80, respectively. Kaplan–Meier and competing risks curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log-rank, both p<0.001). Conclusions 4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support. Usual gait speed measured at hospital discharge is independently associated with adverse outcomes in COPD. Given the simplicity of this test, it should be considered for identification of at-risk patients to enable planning of post-discharge care. https://bit.ly/3g9CvmM
Dosage Compensation in Females with X-Linked Metabolic Disorders

Through the use of new genomic and metabolomic technologies, our comprehension of the molecular and biochemical etiologies of genetic disorders is rapidly expanding, and so are insights into their varying phenotypes. Dosage compensation (lyonization) is an epigenetic mechanism that balances the expression of genes on heteromorphic sex chromosomes. Many studies in the literature have suggested a profound influence of this phenomenon on the manifestation of X-linked disorders in females. In this review, we summarize the clinical and genetic findings in female heterozygotic carriers of a pathogenic variant in one of ten selected X-linked genes whose defects result in metabolic disorders.