Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory Signaling and Brown Fat Activity

Obesity is characterized by a state of chronic inflammation in adipose tissue mediated by the secretion of a range of inflammatory cytokines. In comparison to WAT, relatively little is known about the inflammatory status of brown adipose tissue (BAT) in physiology and pathophysiology. Because BAT and brown/beige adipocytes are specialized in energy expenditure they have protective roles against obesity and associated metabolic diseases. BAT appears to be is less susceptible to developing inflammation than WAT. However, there is increasing evidence that inflammation directly alters the thermogenic activity of brown fat by impairing its capacity for energy expenditure and glucose uptake. The inflammatory microenvironment can be affected by cytokines secreted by immune cells as well as by the brown adipocytes themselves. Therefore, pro-inflammatory signals represent an important component of the thermogenic potential of brown and beige adipocytes and may contribute their dysfunction in obesity.
The Role of PD-1 in Acute and Chronic Infection

PD-1 as an immune checkpoint molecule down-regulates T cell activity during immune responses in order to prevent autoimmune tissue damage. In chronic infections or tumors, lasting antigen-exposure leads to permanent PD-1 expression that can limit immune-mediated clearance of pathogens or degenerated cells. Blocking PD-1 can enhance T cell function; in cancer treatment PD-1 blockade is already used as a successful therapy. However, the role of PD-1 expression and blocking in the context of acute and chronic infections is less defined. Building on its success in cancer therapy leads to the hypothesis that blocking PD-1 in infectious diseases is also beneficial in acute or chronic infections. This review will focus on the role of PD-1 expression in acute and chronic infections with virus, bacteria, and parasites, with a particular focus on recent studies regarding PD-1 blockade in infectious diseases.
Constraints and Perspectives for Sustainable Wheat Production in Tajikistan

Wheat is a major crop with a key role for food security in Tajikistan, contributing 60% of daily calorie intake for the Tajik population. A clear understanding of the major constraints and opportunities relating to wheat production and sustainability in farmers' fields is therefore required. A survey of 210 different wheat fields of different sizes, located in different agricultural zones in Tajikistan and at different altitudes, was conducted during three consecutive years (2012–2014). A questionnaire on wheat production and sustainability, seeking overall information about farms and specific data on crop management practices, was applied. It was accompanied by surveillance of field status concerning diseases, pests, weeds, and influence of abiotic stresses. In addition, a screening was carried out on major Tajik wheat varieties and advanced breeding lines, to assess their resistance to important diseases. The results showed that the agronomic knowledge of Tajik farmers was generally poor and that wheat yield was low, affecting social, economic, and environmental sustainability. The farms surveyed were generally small, growing winter wheat for human consumption year after year. Seeds were hand-broadcast at the optimal sowing time, without chemical treatments and either wheat or technical crops were used as preceding crops. Most farmers used nitrogen fertilizer and irrigation but no weed treatment. The low knowledge status of wheat farmers influenced crop performance and were correlated with lack of crop rotation, while the lack of pest management resulted in high levels of weeds and severe insect damage. While some similarities were shared by most wheat fields surveyed, there was also some variation in wheat crop performance among farms in relation to their size, year of study, agricultural zone, and altitude. Wheat production on small farms still relied heavily on manual labor, while larger farms used more machinery. However, larger farms were not more successful wheat producers than small farms. Most of the Tajik wheat varieties and lines screened were found to be susceptible to at least one of the diseases screened for, i.e., stripe rust, leaf rust, and common bunt. Our findings demonstrate a need for concerted action to overcome wheat yield constraints and achieve sustainability in crop production in Tajikistan. Education of farmers appears key to improving social, economic, and environmental sustainability. Use of certified seed of suitable wheat varieties and appropriate crop management practices, including weed control while also taking biodiversity into consideration, are other important measures for increasing wheat yield and improving sustainability.
Clarification to Commentary: Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis

Citation: Pierce DR, Doma K and Leicht AS (2020) Clarification to Commentary: Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis. Front. Physiol. 11:257. doi: 10.3389/fphys.2020. 00257 Clarification to Commentary: Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis
Mesenchymal Stem Cell Derived Extracellular Vesicles Ameliorate Kidney Injury in Aristolochic Acid Nephropathy

Limitations in the current therapeutic strategies for the prevention of progression of chronic kidney disease (CKD) to end stage renal disease has been a drawback to improving patient recovery. It is therefore imperative that a solution is found to alleviate this problem and improve the health and well-being of patients overall. Aristolochic acid (AA) induced nephropathy, a type of nephrotoxic CKD is characterised by cortical tubular injury, inflammation, leading to interstitial fibrosis. Extracellular vesicles derived from human bone marrow mesenchymal stem cells (MSC-EVs) display therapeutic properties in various disease models including kidney injury. In the current study, we intended to investigate the ability of MSC-EVs on ameliorating tubular injury and interstitial fibrosis in a mouse model of aristolochic acid nephropathy (AAN). The chronic model of AAN is comprised of an intraperitoneal injection of AA in NSG mice, followed by a three-day incubation period and then inoculation of MSC-EVs intravenously. This routine was performed on a weekly basis for four consecutive weeks, accompanied by the monitoring of body weight of all mice. Blood and tissue samples were collected post sacrifice. All animals administered with AA developed kidney injury and renal fibrosis. A gradual loss of body weight was observed, together with a deterioration in kidney function. Although no significant recovery was observed in weight loss following treatment with MSC-EVs, a significant reduction in: blood creatinine and blood urea nitrogen (BUN), tubular necrosis, and interstitial fibrosis was observed. In addition, infiltration of CD45 positive immune cells, fibroblasts, and pericytes which were elevated in the interstitium post AA induced injury, were also significantly reduced by MSC-EVs. Kidneys were also subjected to molecular analyses to evaluate the regulation of pro-fibrotic genes. MSC-EVs significantly reduced AA induction of the pro-fibrotic genes α-Sma, Tgfb1 and Col1a1. A downregulation in pro-fibrotic genes was also observed in fibroblasts activated by AA injured mTECs in vitro. Furthermore, meta-analyses of miRNAs downregulated by MSC-EVs, such as miR21, revealed the regulation of multiple pathways involved in kidney injury including fibrosis, inflammation, and apoptosis. These results therefore suggest that MSC-EVs could play a regenerative and anti-fibrotic role in AAN through the transfer of biologically active cargo that regulates the disease both at a protein and genetic level.
Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia

The mechanistic target of rapamycin (also known as mammalian target of rapamycin) (mTOR)-dependent signaling pathway plays an important role in protein synthesis, cell growth, and proliferation, and has been linked to the development of the central nervous system. Recent studies suggest that mTOR signaling pathway dysfunction could be involved in the etiopathogenesis of schizophrenia. The main goal of this study was to evaluate the status of mTOR signaling pathway in postmortem prefrontal cortex (PFC) samples of subjects with schizophrenia. For this purpose, we quantified the protein expression and phosphorylation status of the mTOR downstream effector ribosomal protein S6 as well as other pathway interactors such as Akt and GSK3β. Furthermore, we quantified the status of these proteins in the brain cortex of rats chronically treated with the antipsychotics haloperidol, clozapine, or risperidone. We found a striking decrease in the expression of total S6 and in its active phosphorylated form phospho-S6 (Ser235/236) in the brain of subjects with schizophrenia compared to matched controls. The chronic treatment with the antipsychotics haloperidol and clozapine affected both the expression of GSK3β and the activation of Akt [phospho-Akt (Ser473)] in rat brain cortex, while no changes were observed in S6 and phospho-S6 (Ser235/236) protein expression with any antipsychotic treatment. These findings provide further evidence for the involvement of the mTOR-dependent signaling pathway in schizophrenia and suggest that a hypofunctional S6 may have a role in the etiopathogenesis of this disorder.
Fecal Microbiota Transplantation in Neurological Disorders

Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.
A Multi-Trait Comparison of an Urban Plant Species Pool Reveals the Importance of Intraspecific Trait Variation and Its Influence on Distinct Functional Responses to Soil Quality

Mounting evidence indicates that the inclusion of intraspecific trait variability (ITV) can strengthen the signal of trait-environment relationships, as well as provide insights into the eco-evolutionary strategies that allow species to establish and persist in different environments. Such information is particularly valuable in urban systems where unique environmental conditions impose strong filtering effects on resident species and where, despite such pressures, high proportions of non-native species persist. In an effort to elucidate functional trait patterns of an urban species pool, we experimentally assessed the effect of soil on trait patterns of 56 plant species collected as seeds from vacant land in Baltimore City, MD, United States. We assessed the relative importance of explained trait variation at different ecological levels by decomposing the variance of six measured traits into three levels: within-species (ITV), between-species (BTV), and across functional groups (FGTV). We then compared functional responses – classified by differences in mean and variance patterns of trait values – across species, traits, and functional groups. Mean trait values varied in response to species and soil (urban vs. potting soil) for all traits, except root ash-free dry mass (AFDM) for soil. Variance decomposition of the species factor into each level showed that variance patterns for species were trait-specific, however, ITV explained a substantial proportion of the total variance for the majority of study traits. When accounting for mean and variance trait patterns between soil types, we found that species with specialized strategies (i.e., C4 photosynthesis and legumes) exhibited functional responses consistent with preadaptation, as defined by no change in the mean or the variance of trait values between soil types, for all traits. Native species showed higher proportions of trait divergence, as defined by shifts in mean trait values between soil types, but not change in variance, relative to introduced species, which showed higher proportions of preadaptation for all traits except specific leaf area (SLA). Species exhibiting trait constriction, or no shift in the mean but a significant change in the variance between soil types, consistently showed decreased variance in urban soil, which supports the idea that urban soils impose strong filtering effects that constrain species trait values. Overall, our study indicates that accounting for ITV, and how it relates to general functional responses associated with changes in the mean and variance of trait values, can provide a clearer understanding of the eco-evolutionary dynamics of plant species in urban environments.
Impact of ex vivo Sample Handling on DNA Methylation Profiles in Human Cord Blood and Neonatal Dried Blood Spots

The profiling of DNA methylation modifications in peripheral blood has significant potential to determine risk factors for human disease. Little is known concerning the sensitivity of DNA methylation profiles to ex vivo sample handling. Here, we studied typical conditions prior to sample storage associated with cord blood samples obtained from clinical investigations using reduced representation bisulfite sequencing. We examined both whole blood collected shortly after birth and dried blood spots, a potentially important source of neonatal blood for investigation of the DNA methylome and the Developmental Origins of Health and Disease in human cohorts because they are routinely collected during clinical care. Samples were matched across different time conditions, as they were from the same cord blood samples obtained from the same individuals. Maintaining whole blood ex vivo up to 24 h (4°C) or dried blood spots up to 7 days (room temp.) had little effect on DNA methylation profiles. Minimal differences were detected between cord blood immediately frozen and dried blood spots. Our results indicate that DNA methylation profiles are resilient to ex vivo sample handling conditions prior to storage. These data will help guide future human studies focused toward determination of DNA methylation modifications in whole blood.
A Survey of Multiple Interactions Between Plants and the Urban Environment

It is well-acknowledged that plants in urban areas provide multiple ecosystem services. They contribute improving ambient quality and mitigating negative impacts of human presence, beautifying the anthropic environment, and promoting place identity and cultural heritage. However, the existence of plants in general, and trees in particular, cannot be considered independent on urban activities and infrastructures. Release of plant volatile compounds is profoundly affected in urban environments, in turn modifying plant relationships with other living organisms, both plants and animals, and affecting air chemistry and quality. Plants also interfere with stone artifacts, cultural and historical heritage. Plant-human coexistence requires precise and adequate managing measures, which have often been ignored in cities' government and planning. Plants and humans (and human infrastructures) are frequently considered as independent from each other and plant requirements are often disregarded, thus causing difficult or erroneous management and/or environmental damage. We review some of the most important ecosystem services provided by plants in urban environment, and also focus on possible negative effects of plants that may become relevant if urban vegetation is improperly managed and unintegrated in proper city planning, both of historical centers and of new towns or suburbs.
Effect of Conscious Sedation vs. General Anesthesia on Outcomes in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke: A Prospective Randomized Clinical Trial

Background: Although several studies have compared conscious sedation (CS) with general anesthesia (GA) in patients undergoing mechanical thrombectomy (MT), there has been no affirmative conclusion. We conducted this trial to assess whether CS is superior to GA for patients undergoing MT for acute ischemic stroke (AIS). Methods: Acute ischemic stroke patients with anterior circulation large vascular occlusion were randomized into two groups. The primary outcome was modified Rankin scale score (0–2) at 90 days after stroke. Secondary outcomes included intraprocedural hemodynamics, time metrics, successful recanalization, neurointerventionalist satisfaction score, National Institutes of Health Stroke Scale (NIHSS) score, and Alberta Stroke Program Early CT Score (ASPECTS) at 48 h post-intervention, mortality at discharge and 3 months after stroke, and complications. Results: Compared with the CS group, heart rate was significantly lower at T1–T8 in the GA group except at T4 (P < 0.05). Mean arterial pressure (MAP) and systolic blood pressure were significantly lower in the GA group at T4–T6 and T9 (P < 0.05). Pulse oxygen saturation was significantly higher at T2–T9 in the GA group (P < 0.05). There were no significant differences in time metrics, vasoactive drug use, occurrence of >20% fall in MAP, pre-recanalization time spent with >20% fall in MAP, neurointerventionalist satisfaction, successful recanalization rate, NIHSS, and ASPECTS scores at 48 h post-intervention, and mortality rate at discharge and 3 months after stroke (P > 0.05). The cerebral infarction rate at 30 days was greater in the CS group, but not significantly (P > 0.05). There were no differences in complication rates except for pneumonia (P > 0.05). Conversion rate from CS to GA was 9.52%. Conclusion: Anesthetic management with GA or CS during MT had no differential impact on the functional outcomes and mortality at discharge or 3 months after stroke in AIS patients, but CS led to more stable hemodynamics and lower incidence of pneumonia.
Plasmodium Perforin-Like Protein Pores on the Host Cell Membrane Contribute in Its Multistage Growth and Erythrocyte Senescence

The pore forming Plasmodium Perforin Like Proteins (PPLP), expressed in all stages of the parasite life cycle are critical for completion of the parasite life cycle. The high sequence similarity in the central Membrane Attack Complex/ Perforin (MACPF) domain among PLPs and their distinct functional overlaps define them as lucrative target for developing multi-stage antimalarial therapeutics. Herein, we evaluated the mechanism of Pan-active MACPF Domain (PMD), a centrally located and highly conserved region of PPLPs, and deciphered the inhibitory potential of specifically designed PMD inhibitors. The E. coli expressed rPMD interacts with erythrocyte membrane and form pores of ~10.5 nm height and ~24.3 nm diameter leading to hemoglobin release and dextran uptake. The treatment with PMD induced erythrocytes senescence which can be hypothesized to account for the physiological effect of disseminated PLPs in loss of circulating erythrocytes inducing malaria anemia. The anti-PMD inhibitors effectively blocked intraerythrocytic growth by suppressing invasion and egress processes and protected erythrocytes against rPMD induced senescence. Moreover, these inhibitors also blocked the hepatic stage and transmission stage parasite development suggesting multi-stage, transmission-blocking potential of these inhibitors. Concievably, our study has introduced a novel set of anti-PMD inhibitors with pan-inhibitory activity against all the PPLPs members which can be developed into potent cross-stage antimalarial therapeutics along with erythrocyte senescence protective potential to occlude PPLPs mediated anemia in severe malaria.
A Review of the Pharmacological Action of Astragalus Polysaccharide

Astragalus membranaceus (A. membranaceus) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to invigorate the spleen and replenish qi. The main components of A. membranaceus are Astragalus polysaccharide (APS), flavonoids compounds, saponins compounds, alkaloids, etc. APS is the most important natural active component in A. membranaceus, and possesses multiple pharmacological properties. At present, APS possess the huge potential to develop a drug improving or treating different diseases. In this review, we reveal the potential approaches of pre-treating and preparation on APS as much as possible and the study on content of APS and its chemical composition including different monosaccharides. More importantly, this paper summarize pharmacological actions on immune regulation, such as enhancing the immune organ index, promoting the proliferation of immune cells, stimulating the release of cytokines, and affecting the secretion of immunoglobulin and conduction of immune signals; anti-aging; anti-tumor by enhancing immunity, inducing apoptosis of tumor cells and inhibiting the proliferation and transfer of tumor cells; antiviral effects; regulation of blood glucose such as type I diabetes mellitus, type II diabetes mellitus and diabetic complications; lipid-lowering; anti-fibrosis; antimicrobial activities and anti-radiation. It provided theoretical basis for the further research such as its structure and mechanism of action, and clinical application of APS.