Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials of inflammatory and autoimmune diseases. Emerging evidence indicates that the immunomodulatory effect of MSCs is primarily attributed to the paracrine pathway. As one of the key paracrine effectors, mesenchymal stem cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm in diameter that play an important role in cell-to-cell communication by carrying bioactive substances from parental cells. Recent studies support the finding that MSC-EXOs have an obvious inhibitory effect toward different effector cells involved in the innate and adaptive immune response. Moreover, substantial progress has been made in the treatment of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSC-EXOs are capable of reproducing MSC function and overcoming the limitations of traditional cell therapy. Therefore, using MSC-EXOs instead of MSCs to treat autoimmune diseases appears to be a promising cell-free treatment strategy. In this review, we review the current understanding of MSC-EXOs and discuss the regulatory role of MSC-EXOs on immune cells and its potential application in autoimmune diseases.
Overview of the Mechanisms of Action of Selected Bisphenols and Perfluoroalkyl Chemicals on the Male Reproductive Axes

Male fertility has been deteriorating worldwide for considerable time, with the greatest deterioration recorded mainly in the United States, Europe countries, and Australia. That is, especially in countries where an abundance of chemicals called endocrine disruptors has repeatedly been reported, both in the environment and in human matrices. Human exposure to persistent and non-persistent chemicals is ubiquitous and associated with endocrine-disrupting effects. This group of endocrine disrupting chemicals (EDC) can act as agonists or antagonists of hormone receptors and can thus significantly affect a number of physiological processes. It can even negatively affect human reproduction with an impact on the development of gonads and gametogenesis, fertilization, and the subsequent development of embryos. The negative effects of endocrine disruptors on sperm gametogenesis and male fertility in general have been investigated and repeatedly demonstrated in experimental and epidemiological studies. Male reproduction is affected by endocrine disruptors via their effect on testicular development, impact on estrogen and androgen receptors, potential epigenetic effect, production of reactive oxygen species or direct effect on spermatozoa and other cells of testicular tissue. Emerging scientific evidence suggests that the increasing incidence of male infertility is associated with the exposure to persistent and non-persistent endocrine-disrupting chemicals such as bisphenols and perfluoroalkyl chemicals (PFAS). These chemicals may impact men’s fertility through various mechanisms. This study provides an overview of the mechanisms of action common to persistent (PFAS) and nonpersistent (bisphenols) EDC on male fertility.
Mitochondrial Regulation of Diabetic Kidney Disease

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement on future targeted therapies based on improving mitochondrial function in DKD. This review will highlight the latest advances in understanding the nature of mitochondria dysfunction and its role in progression of DKD, and the development of mitochondrial targets that could be potentially used to prevent its progression.
Short-Term Association of Air Pollutant Levels and Hospital Admissions for Stroke and Effect Modification by Apparent Temperature: Evidence From Shanghai, China

The epidemiological evidence on relationships between air pollution, temperature, and stroke remains inconclusive. Limited evidence is available for the effect modification by apparent temperature, an indicator reflecting reactions to the thermal environment, on short-term associations between air pollution and hospital admissions for stroke. We used a generalized additive model with Poisson regression to estimate the relative risk (RR) of stroke admissions in Shanghai, China, between 2014 and 2016 associated with air pollutants, with subgroup analyses by age, sex, apparent temperature, and season. During the study period, changes in the daily number of stroke admissions per 10 μg/m3 increase in nitrogen dioxide (at lags 0, 1, 0–1, and 0–2) ranged from 1.05 (95% CI: 0.82%, 2.88%) to 2.24% (95% CI: 0.84%, 3.65%). For each 10 μg/m3 increase in sulfur dioxide concentrations at lags 1, 2, 0–1, and 0–2, the RR of daily stroke admissions increased by 3.34 (95% CI: 0.955%, 5.79%), 0.32 (95% CI: −1.97%, 2.67%), 3.33 (95% CI: 0.38%, 6.37%), and 2.86% (95% CI: −0.45%, 6.28%), respectively. The associations of same-day exposure to nitrogen dioxide with stroke admissions remained significant after adjustment for ozone levels. These associations were not modified by sex, age, apparent temperature, or season. More research is warranted to determine whether apparent temperature modifies the associations between air pollution and stroke admissions.
MDMA-Assisted Therapy as a Means to Alter Affective, Cognitive, Behavioral, and Neurological Systems Underlying Social Dysfunction in Social Anxiety Disorder

Social anxiety disorder (SAD) is a prevalent and often debilitating psychiatric disorder that can assume a chronic course even when treated. Despite the identification of evidence-based pharmacological and behavioral treatments for SAD, much room for improved outcomes exists and 3,4-methylenedioxymethamphetamine (MDMA) has been proposed as a promising adjunctive treatment to psychological interventions for disorders characterized by social dysfunction. A small randomized, placebo-controlled trial of MDMA-assisted therapy (MDMA-AT) for social anxiety in autistic adults offered encouraging results, but more research is sorely needed to explore the potential for MDMA-AT in treating SAD. This review aims to stimulate future study by summarizing research on disruptions in neurological, perceptual, receptive, and expressive systems regulating social behavior in SAD and proposing how MDMA-AT may alter these systems across four domains. First, we review research highlighting the roles of social anhedonia and reduced social reward sensitivity in maintaining SAD, with specific attention to the reduction in positive affect in social situations, infrequent social approach behaviors, and related social skills deficits. We posit that MDMA-AT may enhance motivation to connect with others and alter perceptions of social reward for an extended period following administration, thereby potentiating extinction processes, and increasing the reinforcement value of social interactions. Second, we review evidence for the central role of heightened social evaluative threat perception in the development and maintenance of SAD and consider how MDMA-AT may enhance experiences of affiliation and safety when interacting with others. Third, we consider the influence of shame and the rigid application of shame regulation strategies as important intrapersonal processes maintaining SAD and propose the generation of self-transcendent emotions during MDMA sessions as a mechanism of shame reduction that may result in corrective emotional experiences and boost memory reconsolidation. Finally, we review research on the role of dysfunctional interpersonal behaviors in SAD that interfere with social functioning and, in particular, the development and maintenance of close and secure relationships. We discuss the hypothesized role of MDMA-AT in improving social skills to elicit positive interpersonal responses from others, creating a greater sense of belonging, acceptance, and social efficacy.
Precision Medicine in Mite Allergic Rhinitis

It is well-known that a correct diagnosis is necessary for effective treatment. In the case of allergic rhinitis due to mites, imprecise diagnosis with effective but improvable methods means that in many cases an optimal result is not reached in patients. The diagnosis of allergic rhinitis due to mite sensitization have to require more homogeneously reproducible diagnostic tests that try to encompass many more of the protein antigens contained in them. With the few proteins that the problem has usually focused on, there is no they would cover many of the clinically relevant allergens in a large proportion of patients. In this mini-review we try to highlight the importance of having good allergenic sources and briefly gather information on various allergenic proteins included in mites that could be clinically relevant. All this to try to get closer to a more accurate diagnosis. We are also talking about two diagnostic tools that are clearly out of use and that should be promoted in the consultations to obtain an even greater and better outcome in patients.
Revisiting the Immunological Aspects of Temozolomide Considering the Genetic Landscape and the Immune Microenvironment Composition of Glioblastoma

The microenvironment (ME) plays a critical role in causing glioblastoma (GBM) to be a moving and incurable target. The main features governing the interaction between cancer cells and the ME include dependency, promotion, and in rare cases, even competition. In the original Stupp protocol, the alkylating agent temozolomide (TMZ) is the first-line chemotherapy drug to treat GBM, and it is broadly used together or after radiotherapy. Some studies have described TMZ as an adjuvant to other therapeutic approaches including immunotherapy because of its ability to induce an immunogenic death of cancer cells. TMZ also exerts immunomodulatory effects on the tumor and immune ME. These findings support the coexistence of two circuits, i.e., one that subverts local immunosuppressive mechanisms and another that exerts a harmful influence on the peripheral immune response. A bias toward the latter can drive the failure of treatments based on the combination of chemotherapy and immunotherapy approaches. In this review, we will reanalyze how intrinsic and acquired resistance to TMZ impacts the immunomodulatory effects previously described by way of inducing a functional alteration of local immune cells and promoting immunosuppression and how different components of the immune ME, with particular attention to tumor-associated macrophages and microglia, can cause TMZ resistance to circumvent potential local immunogenic mechanisms.
Ursolic Acid Targets Glucosyltransferase and Inhibits Its Activity to Prevent Streptococcus mutans Biofilm Formation

Streptococcus mutans (S. mutans), the prime pathogen of dental caries, can secrete glucosyltransferases (GTFs) to synthesize extracellular polysaccharides (EPSs), which are the virulence determinants of cariogenic biofilms. Ursolic acid, a type of pentacyclic triterpene natural compound, has shown potential antibiofilm effects on S. mutans. To investigate the mechanisms of ursolic acid-mediated inhibition of S. mutans biofilm formation, we first demonstrated that ursolic acid could decrease the viability and structural integrity of biofilms, as evidenced by XTT, crystal violet, and live/dead staining assays. Then, we further revealed that ursolic acid could compete with the inherent substrate to occupy the catalytic center of GTFs to inhibit EPS formation, and this was confirmed by GTF activity assays, computer simulations, site-directed mutagenesis, and capillary electrophoresis (CE). In conclusion, ursolic acid can decrease bacterial viability and prevent S. mutans biofilm formation by binding and inhibiting the activity of GTFs.
Formulating and Deploying Strength Amplification Controllers for Lower-Body Walking Exoskeletons

Augmenting the physical strength of a human operator during unpredictable human-directed (volitional) movements is a relevant capability for several proposed exoskeleton applications, including mobility augmentation, manual material handling, and tool operation. Unlike controllers and augmentation systems designed for repetitive tasks (e.g., walking), we approach physical strength augmentation by a task-agnostic method of force amplification—using force/torque sensors at the human–machine interface to estimate the human task force, and then amplifying it with the exoskeleton. We deploy an amplification controller that is integrated into a complete whole-body control framework for controlling exoskeletons that includes human-led foot transitions, inequality constraints, and a computationally efficient prioritization. A powered lower-body exoskeleton is used to demonstrate behavior of the control framework in a lab environment. This exoskeleton can assist the operator in lifting an unknown backpack payload while remaining fully backdrivable.
Prevalence and Associated Factors of Suicidal Behavior Among Patients and Residents in Northwest Ethiopia

There are a million suicide deaths in the world annually, and 75% of these occur in low- and middle-income countries (LMICs). However, there are limited resources to prevent suicidal deaths in those regions. The aim was to assess the prevalence of suicidal behavior and associated factors among patients visiting for medical care at a health center and residents in the community. A comparative study was employed by interviewing 2,625 residents in the community and 1,363 patients at the health center about suicidal behavior in northwest Ethiopia, from March 2017 to February 2018. Logistic analysis was employed with adjusted odds ratios and 95% confidence interval (CI) and with p-value < 0.05. The total prevalence of suicidal behavior (ideation, plan, and attempt) was found to be 5.6% (with 95% CI range 5–6%). It was found to be 4.4% with 95% CI range 4–5% in residents and 7.9% with 95% CI range 6–9% in patients. Female sex, depressive symptoms, physical/verbal abuse, and feeling stigmatized were identified as a risk factors for suicidal behavior, whereas a healthy lifestyle, such as eating regular meals of fruits and vegetables, doing physical exercise regularly, and having public health insurance were identified as protective risk factors for suicidal behavior even after adjusting for being a patient or not. The proportion of suicidal behavior was double in patients compared with residents. Suicidal behavior should be assessed in patients who visit for medical help and integration of mental health service within the primary health care system is recommended, especially in low-income countries.
The Era of Antimicrobial Peptides: Use of Hepcidins to Prevent or Treat Bacterial Infections and Iron Disorders

The current treatments applied in aquaculture to limit disease dissemination are mostly based on the use of antibiotics, either as prophylactic or therapeutic agents, with vaccines being available for a limited number of fish species and pathogens. Antimicrobial peptides are considered as promising novel substances to be used in aquaculture, due to their antimicrobial and immunomodulatory activities. Hepcidin, the major iron metabolism regulator, is found as a single gene in most mammals, but in certain fish species, including the European sea bass (Dicentrarchus labrax), two different hepcidin types are found, with specialized roles: the single type 1 hepcidin is involved in iron homeostasis trough the regulation of ferroportin, the only known iron exporter; and the various type 2 hepcidins present antimicrobial activity against a number of different pathogens. In this study, we tested the administration of sea bass derived hepcidins in models of infection and iron overload. Administration with hamp2 substantially reduced fish mortalities and bacterial loads, presenting itself as a viable alternative to the use of antibiotics. On the other hand, hamp1 seems to attenuate the effects of iron overload. Further studies are necessary to test the potential protective effects of hamp2 against other pathogens, as well as to understand how hamp2 stimulate the inflammatory responses, leading to an increased fish survival upon infection.
A Novel and Rapid Serum Detection Technology for Non-Invasive Screening of Gastric Cancer Based on Raman Spectroscopy Combined With Different Machine Learning Methods

Gastric cancer (GC) is the fifth most common cancer in the world and a serious threat to human health. Due to its high morbidity and mortality, a simple, rapid and accurate early screening method for GC is urgently needed. In this study, the potential of Raman spectroscopy combined with different machine learning methods was explored to distinguish serum samples from GC patients and healthy controls. Serum Raman spectra were collected from 109 patients with GC (including 35 in stage I, 14 in stage II, 35 in stage III, and 25 in stage IV) and 104 healthy volunteers matched for age, presenting for a routine physical examination. We analyzed the difference in serum metabolism between GC patients and healthy people through a comparative study of the average Raman spectra of the two groups. Four machine learning methods, one-dimensional convolutional neural network, random forest, support vector machine, and K-nearest neighbor were used to explore identifying two sets of Raman spectral data. The classification model was established by using 70% of the data as a training set and 30% as a test set. Using unseen data to test the model, the RF model yielded an accuracy of 92.8%, and the sensitivity and specificity were 94.7% and 90.8%. The performance of the RF model was further confirmed by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.9199. This exploratory work shows that serum Raman spectroscopy combined with RF has great potential in the machine-assisted classification of GC, and is expected to provide a non-destructive and convenient technology for the screening of GC patients.
Trace Element (Fe, Co, Ni and Cu) Dynamics Across the Salinity Gradient in Arctic and Antarctic Glacier Fjords

Around the Greenlandic and Antarctic coastlines, sediment plumes associated with glaciers are significant sources of lithogenic material to the ocean. These plumes contain elevated concentrations of a range of trace metals, especially in particle bound phases, but it is not clear how these particles affect dissolved (<0.2 µm) metal distributions in the ocean. Here we show, using transects in 8 glacier fjords, trends in the distribution of dissolved iron, cobalt, nickel and copper (dFe, dCo, dNi, dCu). Following rapid dFe loss close to glacier outflows, dFe concentrations in particular showed strong similarities between different fjords. Similar dFe concentrations were also observed between seasons/years when Nuup Kangerlua (SW Greenland) was revisited in spring, mid- and late-summer. Dissolved Cu, dCo and dNi concentrations were more variable and showed different gradients with salinity depending on the fjord, season and year. The lack of consistent trends for dCu and dNi largely reflects less pronounced differences contrasting the concentration of inflowing shelf waters with fresher glacially-modified waters. Particles also made only small contributions to total dissolvable Cu (dCu constituted 83 ± 28% of total dissolvable Cu) and Ni (dNi constituted 86 ± 28% of total dissolvable Ni) within glacier plumes. For comparison, dFe was a lower fraction of total dissolvable Fe; 3.5 ± 4.8%. High concentrations of total dissolvable Fe in some inner-fjord environments, up to 77 µM in Ameralik (SW Greenland), may drive enhanced removal of scavenged type elements, such as Co. Further variability may have been driven by local bedrock mineralogy, which could explain high concentrations of dNi (25–29 nM) and dCo (6–7 nM) in one coastal region of west Greenland (Kangaatsiaq). Our results suggest that dissolved trace element distributions in glacier fjords are influenced by a range of factors including: freshwater concentrations, local geology, drawdown by scavenging and primary production, saline inflow, and sediment dynamics. Considering the lack of apparent seasonality in dFe concentrations, we suggest that fluxes of some trace elements may scale proportionately to fjord overturning rather than directly to freshwater discharge flux.
WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway

Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported. Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy. Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments. Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway. Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway.