Miracle-dz/UniFAR-FTUs huggingface dataset:
Nose-Only Water-Pipe Smoke Exposure in Mice Elicits Renal Histopathological Alterations, Inflammation, Oxidative Stress, DNA Damage, and Apoptosis

The prevalence of water-pipe tobacco smoking is increasing worldwide, and is relatively high among youth and young adults. Exposure to water-pipe smoke (WPS) has been reported to affect various systems including the respiratory, cardiovascular and reproductive systems. However, the impact of WPS exposure on the kidney has received only scant attention. Here, we assessed the effect of nose-only WPS exposure for one or four consecutive weeks on renal histology, inflammation, oxidative stress, DNA damage, and apoptosis. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Light and electron microcopy analysis revealed that the WPS exposure (especially at 4-week time point) caused degeneration of the endothelial cells of the glomerular capillaries and vacuolar degenerations of the proximal convoluted tubules. WPS exposure also significantly decreased the creatinine clearance, and significantly increased proteinuria and urinary kidney injury molecule-1 (KIM-1) concentration. Kidney lipid peroxidation, reactive oxygen species, and oxidized glutathione were significantly increased. WPS exposure also affected the concentration of reduced glutathione and the activity of catalase. Likewise, renal concentrations of interleukin (IL)-6, IL-1β and KIM-1 were augmented by WPS exposure. Moreover, WPS caused DNA damage as evaluated by comet assay, and increased the expression of cleaved caspase-3 and cytochrome C in the kidney. We conclude that exposure of mice to WPS caused renal histopathological alterations, inflammation, oxidative stress, DNA damage, and apoptosis. If the latter findings could be substantiated by controlled human studies, it would be an additional cause for disquiet about an established public health concern.
Measurement of Platelet Function in an Experimental Stroke Model With Aspirin and Clopidogrel Treatment

Dual antiplatelet treatment (DAPT) increases the risk of tPA-associated hemorrhagic transformation (HT) in ischemic stroke. To investigate the effects of DAPT in rodents, reliable indicators of platelet function utilizing a minimally invasive procedure are required. We here established a fluorescence-based assay to monitor DAPT efficiency in a mouse model of ischemic stroke with HT. Male C57/BL6 mice were fed with aspirin and clopidogrel (ASA+CPG). Venous blood was collected, stimulated with thrombin, labeled with anti-CD41-FITC and anti-CD62P-PE, and analyzed by flow cytometry. Subsequently, animals were subjected to experimental stroke and tail bleeding tests. HT was quantified using NIH ImageJ software. In ASA+CPG mice, the platelet activation marker CD62P was reduced by 40.6 ± 4.2% (p < 0.0001) compared to controls. In vitro platelet function correlated inversely with tail bleeding tests (r = −0.8, p = 0.0033, n = 12). Twenty-four hours after drug withdrawal, platelet activation rates in ASA+CPG mice were still reduced by 20.2 ± 4.1% (p = 0.0026) compared to controls, while tail bleeding volumes were increased by 4.0 ± 1.4 μl (p = 0.004). Conventional tests using light transmission aggregometry require large amounts of blood and thus cannot be used in experimental stroke studies. In contrast, flow cytometry is a highly sensitive method that utilizes small volumes and can easily be incorporated into the experimental stroke workflow. Our test can be used to monitor the inhibitory effects of DAPT in mice. Reduced platelet activation is indicative of an increased risk for tPA-associated cerebral hemorrhage following experimental stroke. The test can be applied to individual animals and implemented flexibly prior and subsequent to experimental stroke.
Pores for Thought: Can Genetic Manipulation of Stomatal Density Protect Future Rice Yields?

Rice (Oryza sativa L.) contributes to the diets of around 3.5 billion people every day and is consumed more than any other plant. Alarmingly, climate predictions suggest that the frequency of severe drought and high-temperature events will increase, and this is set to threaten the global rice supply. In this review, we consider whether water or heat stresses in crops — especially rice — could be mitigated through alterations to stomata; minute pores on the plant epidermis that permit carbon acquisition and regulate water loss. In the short-term, water loss is controlled via alterations to the degree of stomatal “openness”, or, in the longer-term, by altering the number (or density) of stomata that form. A range of molecular components contribute to the regulation of stomatal density, including transcription factors, plasma membrane-associated proteins and intercellular and extracellular signaling molecules. Much of our existing knowledge relating to stomatal development comes from research conducted on the model plant, Arabidopsis thaliana. However, due to the importance of cereal crops to global food supply, studies on grass stomata have expanded in recent years, with molecular-level discoveries underscoring several divergent developmental and morphological features. Cultivation of rice is particularly water-intensive, and there is interest in developing varieties that require less water yet still maintain grain yields. This could be achieved by manipulating stomatal development; a crop with fewer stomata might be more conservative in its water use and therefore more capable of surviving periods of water stress. However, decreasing stomatal density might restrict the rate of CO2 uptake and reduce the extent of evaporative cooling, potentially leading to detrimental effects on yields. Thus, the extent to which crop yields in the future climate will be affected by increasing or decreasing stomatal density should be determined. Here, our current understanding of the regulation of stomatal development is summarised, focusing particularly on the genetic mechanisms that have recently been described for rice and other grasses. Application of this knowledge toward the creation of “climate-ready” rice is discussed, with attention drawn to the lesser-studied molecular elements whose contributions to the complexity of grass stomatal development must be understood to advance efforts.
Novel P-n Li2SnO3/g-C3N4 Heterojunction With Enhanced Visible Light Photocatalytic Efficiency Toward Rhodamine B Degradation

The design of highly efficient and stable photocatalysts to utilize solar energy is a significant challenge in photocatalysis. In this work, a series of novel p-n heterojunction photocatalysts, Li2SnO3/g-C3N4, was successfully prepared via a facile calcining method, and exhibited superior photocatalytic activity toward the photodegradation of Rhodamine B solution under visible light irradiation as compared with pure Li2SnO3 and g-C3N4. The maximum kinetic rate constant of photocatalytic degradation of Rhodamine B within 60 min was 0.0302 min−1, and the composites still retained excellent performance after four successive recycles. Chemical reactive species trapping experiments and electron paramagnetic resonance demonstrated that hydroxyl radicals (·OH) and superoxide ions (·O2-) were the dominant active species in the photocatalytic oxidation of Rhodamine B solution, while holes (h+) only played a minor role. We demonstrated that the enhancement of the photocatalytic activity could be assigned to the formation of a p-n junction photocatalytic system, which benefitted the efficient separation of photogenerated carriers. This study provides a visible light-responsive heterojunction photocatalyst with potential applications in environmental remediation.
Population Survey Data Informing the Therapeutic Potential of Classic and Novel Phenethylamine, Tryptamine, and Lysergamide Psychedelics

Introduction The majority of contemporary psychedelic research has focused on ayahuasca, lysergic acid diethylamide, and psilocybin, though there are hundreds of novel psychedelic compounds that may have clinical utility. The purpose of the present study was to evaluate the therapeutic potential of classic and novel phenethylamine, tryptamine, and lysergamide psychedelics via a large, nationally representative population-based survey. Methods We tested the unique associations of lifetime classic and novel phenethylamine, tryptamine, and lysergamide psychedelics with past month psychological distress and past year suicidality among respondents pooled from years 2008–2017 of the National Survey on Drug Use and Health (weighted N = 260,964,827). Results Lifetime classic tryptamine use was associated with a decreased odds of past month psychological distress [aOR = 0.76; (0.69–0.83)] and past year suicidal thinking [aOR = 0.79; (0.72–0.87)]. Lifetime novel phenethylamine use, on the other hand, was associated with an increased odds of past year suicidal thinking [aOR = 1.44; (1.06–1.95)] and past year suicidal planning [aOR = 1.60; (1.06–2.41)]. No other significant associations were found. Discussion and Conclusions These findings, which may be driven by differences in pharmacodynamics, suggest that classic tryptamines may hold the greatest therapeutic potential of the psychedelics, whereas novel phenethylamines may pose risk for harm. The present findings thus support continued research on the clinical application of classic tryptamines. Though the current results caution against the clinical utility of novel phenethylamines, further study of these and other novel psychedelic substances is nonetheless warranted to better understand their potential application.
Irradiation Induces Epithelial Cell Unjamming

The healthy and mature epithelial layer is ordinarily quiescent, non-migratory, solid-like, and jammed. However, in a variety of circumstances the layer transitions to a phase that is dynamic, migratory, fluid-like and unjammed. This has been demonstrated in the developing embryo, the developing avian airway, the epithelial layer reconstituted in vitro from asthmatic donors, wounding, and exposure to mechanical stress. Here we examine the extent to which ionizing radiation might similarly provoke epithelial layer unjamming. We exposed primary human bronchial epithelial (HBE) cells maintained in air-liquid interface (ALI) to sub-therapeutic doses (1 Gy) of ionizing radiation (IR). We first assessed: (1) DNA damage by measuring p-H2AX, (2) the integrity of the epithelial layer by measuring transepithelial electrical resistance (TEER), and (3) the extent of epithelial cell differentiation by detecting markers of differentiated airway epithelial cells. As expected, IR exposure induced DNA damage but, surprisingly, disrupted neither normal differentiation nor the integrity of the epithelial cell layer. We then measured cell shape and cellular migration to determine the extent of the unjamming transition (UJT). IR caused cell shape elongation and increased cellular motility, both of which are hallmarks of the UJT as previously confirmed. To understand the mechanism of IR-induced UJT, we inhibited TGF-β receptor activity, and found that migratory responses were attenuated. Together, these observations show that IR can provoke epithelial layer unjamming in a TGF-β receptor-dependent manner.
Involvement of Heme in Colony Spreading of Staphylococcus aureus

Staphylococcus aureus spreads rapidly on the surface of soft agar medium. The spreading depends on the synthesis of biosurfactants, i.e., phenol soluble modulins (PSMs), which facilitate colony spreading of S. aureus. Our earlier study demonstrated that water accumulates in a colony is important to modulate colony spreading of S. aureus. The current study screened a transposon-based mutant library of S. aureus HG001 and obtained four non-spreading mutants with mutations in hemY and ctaA, which are involved in heme synthesis. The spreading ability of these mutants was restored when the mutants are transformed with a plasmid encoding hemY or ctaA, respectively. HemY mutants, which do not synthesize heme B, were able to spread on agar medium supplemented with hemin, a heme B derivative. By contrast, hemin supplementation did not rescue the spreading of the ctaA mutant, which lacks heme B and heme A, indicating that heme A is also critical for colony spreading. Moreover, mutations in hemY and ctaA had little effect on PSMs production but affect ATP production and water accumulation in the colony. In conclusion, this study sheds light on the role of heme synthesis and energy production in the regulation of S. aureus colony spreading, which is important for understanding the movement mechanisms of bacteria lacking a motor apparatus.
Pregabalin Abuse in Combination With Other Drugs: Monitoring Among Methadone Patients

Introduction In recent years, there has been an increase in the non-medical use of psychoactive prescription drugs including pregabalin (PGB). Studies have shown that multiple drug users and patients in methadone treatment programs administered PGB at high dosages in order to achieve euphoria, reduce withdrawal symptoms, or potentiate the effects of methadone. For these reasons, accurate toxicological monitoring is required for these high-risk individuals. Materials and Methods The present study investigated whether PGB could be detected in the hair samples of 250 patients with a history of opiate dependency, and under toxicological surveillance assess their compliance with methadone maintenance therapy. Results Opiates were found in 54/250 of all hair samples, while cannabis was present in 74/250 patients, cocaine was detected in 21/250 patients, and benzodiazepines without prescription were identified in 49/250 patients. As expected, methadone was present in all 250 patients (100%). PGB without prescription was found in the hair samples of 35/250 patients (14%). Of these, 91.43% were male, 48.57% were <30 y old, and 45.71% were between ages 30 and 50 y. There were no apparent associations among PGB use, daily methadone dosage, and duration of methadone maintenance therapy. Psychiatric comorbidities were present in 25.71% of the patients abusing PGB. Anxiety (55.56%) and depression (33.33%) were the most prevalent psychiatric disorders. Discussion Most of the patients taking PGB (57.14%) used other drugs (especially opiates) concurrently. The utility of hair analysis is explained by easy and rapid sample collection and the ability of the hair to reflect long-term drug use and incorporate drug metabolites. The findings of this study suggested that PGB has significant potential for abuse by high-risk populations such as opioid users and patients with dual diagnosis. These risks are particularly high in cases of poly-drug use and drug intake that are not in compliance with prescription guidelines.
Ethical Issues in Online Psychotherapy: A Narrative Review

Background The provision of psychotherapy over distance using technology is a growing market reaching many patients and therefore the risks and benefits need to be known by all psychotherapists whether they themselves practice online or not. This comprehensive review of the main ethical arguments for and against different forms of online psychotherapy aims to enhance discussion of ethical issues in this growing area. Methods A search of three databases (PubMed, PsycINFO, Web of Science) was conducted in August 2019 using a specific search protocol yielding 249 publications. Results Of 24 ethical arguments in favor of online psychotherapy and 32 against, the top five ethical arguments in favor of online psychotherapy were (1) increased access to psychotherapy and service availability and flexibility; (2) therapy benefits and enhanced communication; (3) advantages related to specific client characteristics (e.g. remote location); (4) convenience, satisfaction, acceptance, and increased demand; and (5) economic advantages. The top five ethical arguments against engagement in online psychotherapy were (1) privacy, confidentiality, and security issues; (2) therapist competence and need for special training; (3) communication issues specific to technology; (4) research gaps; and (5) emergency issues. Conclusions The findings may be of help to practitioners in deciding whether to engage in online psychotherapy, and in informing patients about risks and benefits, improving ethical guidelines, and stimulating further ethical discussion. The findings are argumentative and qualitative in nature, and further quantitative research is needed.
Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.
Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pulmonary lobe were isolated and cultured in vitro. Establishment of hypoxic pulmonary hypertension model in wild type and TG2 knockout mice. SERCA2 serotonylation was analyzed by co-(immunoprecipitation) IP when the TG2 gene silenced or overexpressed under normoxia and hypoxia in vivo and in vitro. Intracellular calcium ion was measured by using Fluo-4AM probe under normoxia and hypoxia. Real-time (RT)-PCR and Western blot analyzed expression of TG2, TRPC1, and TRPC6 under normoxia and hypoxia. Bioactivity of cells were analyzed by using Cell Counting Kit (CCK)-8, flow cytometry, wound healing, RT-PCR, and Western blot under PST-2744 and cyclopiazonic acid. We confirmed that 1) hypoxia enhanced the expression and activity of TG2, and 2) hypoxia increased the basal intracellular Ca2+ concentration ([Ca2+]i) and SOCE through activating TRPC6 on human pulmonary vein smooth muscle cells (hPVSMC). Then, we investigated the effects of overexpression and downregulation of the TG2 gene on the activity of SERCA2, s-SERCA2, basal [Ca2+]i, and SOCE under normoxia and hypoxia in vitro, and investigated the activity of SERCA2 and s-SERCA2 in vivo, respectively. We confirmed that SERCA2 serotonylation inhibited the activity of SERCA2 and increased the Ca2+ influx, and that hypoxia induced TG2-mediated SERCA2 serotonylation both in vivo and in vitro. Furthermore, we investigated the effect of TG2 activity on the biological behavior of hPVSMC by using an inhibitor and agonist of SERCA2, respectively. Finally, we confirmed that chronic hypoxia cannot increase vessel wall thickness, the right ventricular systolic pressure (RVSP), and right ventricular hypertrophy index (RVHI) of vascular smooth muscle-specific Tgm2−/− mice. These results indicated that hypoxia promoted TG2-mediated SERCA2 serotonylation, thereby leading to inhibition of SERCA2 activity, which further increased the calcium influx through the TRPC6 channel. Furthermore, tissue-specific conditional TG2 knockout mice prevents the development of pulmonary hypertension caused by hypoxia. In summary, we uncovered a new target (TG2) for treatment of chronic hypoxic pulmonary hypertension (CHPH).
A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy

The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Further, the expressions of complements and several other key pro- and anti-angiogenic genes in the serum and vitreous humor were analyzed in the blood samples of PDR and non-PDR (NPDR) patients along with controls without diabetes. We also assessed the pro-inflammatory cytokines and matrix metalloproteinases in the vitreous humor samples. There was a significant increase in C3 and its activated fragment C3bα' (110 kDa) along with a corresponding upregulation of CFH in the vitreous of PDR patients, which confirmed the increased activation of the alternative complement pathway in PDR. Likewise, a significant upregulation of angiogenic genes and downregulation of anti-angiogenic genes was seen in PDR and NPDR cases. Increased MMP9 activity and upregulation of inflammatory markers IL8 and sPECAM with a downregulation of anti-inflammatory marker IL-10 in PDR vitreous indicated the possible involvement of microglia in DR pathogenesis. Further, a significantly high C3 deposition in the capillary wall along with thickening of basement membranes and co-localization of CFH expression with CD11b+ve activated microglial cells in diabetic retina suggested microglia as a source of CFH in diabetic retina. The increased CFH levels could be a feedback mechanism for arresting excessive complement activation in DR eyes. A gradual increase of CFH and CD11b expression in retina with early to late changes in epiretinal membranes of DR patients indicated a major role for the alternative complement pathway in disease progression.