Miracle-dz/UniFAR-FTUs huggingface dataset:
Soft Malleable Vesicles: versatile carriers for efficient topical delivery of fungal therapeutics

Abstract Fungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.
A Green Sulfur Bacterium From Epsomitic Hot Lake, Washington, USA.

Hot Lake is a small heliothermal and hypersaline lake in far north-central Washington State (USA) and is limnologically unusual because MgSO4 rather than NaCl is the dominant salt. In late summer, the Hot Lake metalimnion becomes distinctly green from blooms of planktonic phototrophs. In a study undertaken over 60 years ago, these blooms were predicted to include green sulfur bacteria but no cultures were obtained. We sampled Hot Lake and established enrichment cultures for phototrophic sulfur bacteria in MgSO4-rich sulfidic media. Most enrichments turned green or red within two weeks, and from green-colored enrichments, pure cultures of a lobed green sulfur bacterium (Phylum Chlorobi) were isolated. Phylogenetic analyses showed the organism to be a species of the prosthecate green sulfur bacterium Prosthecochloris. Cultures of this Hot Lake phototroph were halophilic and tolerated high levels of sulfide and MgSO4. In addition, unlike all recognized species of Prosthecochloris, the Hot Lake isolates grew at temperatures up to 45°C, indicating an adaptation to the warm summer temperatures of the lake. Photoautotrophy by Hot Lake green sulfur bacteria may contribute dissolved organic matter to anoxic zones of the lake, and their diazotrophic capacity may provide a key source of bioavailable nitrogen, as well.
Low‐density lipoproteins protect sperm during cryopreservation in buffalo: Unraveling mechanism of action

This study was carried out to reveal factors and the mechanism of action by which low‐density lipoproteins (LDLs) protect sperm better than egg yolk (EY) during cryopreservation. We extracted LDL from EY and compared the amount of calcium, progesterone, and antioxidants in EY and LDL. We found a very high concentration of progesterone (1423.95 vs. 10.46 ng/ml) and calcium (29.19 vs. 0.47 mM) in EY as compared with LDL. Antioxidant assays like DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) and the ferric reducing antioxidants power assay revealed that the LDL extender had almost double ability to lose hydrogen than the EY extender. For sperm cryopreservation, 20 ejaculates from four Murrah buffalo bulls were collected. Each ejaculate was divided into four aliquots and extended in 10%, 12%, and 14% LDL (w/v) and EY‐based extenders, followed by cryopreservation. The LDL‐based extender prevented excessive cholesterol efflux, and its high content of antioxidants minimized reactive oxygen species generated during cryopreservation, resulting in a functional CatSper channel. The EY‐based extender promoted excess cholesterol efflux due to the presence of high‐density lipoprotein, resulting in a compromised CatSper channel. High intracellular calcium in a cryopreserved sperm in the EY group as compared with the LDL group indicates that progesterone present in EY activates the CatSper channel, resulting in a heavy calcium influx into the sperm. The greater tyrosine phosphorylation and increased number of F‐pattern in the sperm cryopreserved in the EY extender indicate that high intracellular calcium triggers more capacitation‐like changes in the sperm cryopreserved in EY than LDL extender. In conclusion, we demonstrated the new facts and understandings about LDL and EY for semen cryopreservation.
Effect and Relationship of Seasons on the High Risk of Ovarian Hyperstimulation Syndrome After Oocyte Retrieval in Patients With Polycystic Ovary Syndrome

Objective To investigate the effect of seasons on the incidence of high risk of ovarian hyperstimulation syndrome (OHSS) after in oocyte retrieval in patients with polycystic ovarian syndrome (PCOS) and to establish a nomogram to predict the risk of OHSS. Design Single-center, retrospective study. Setting University-affiliated reproductive medicine center. Patient(s) A total of 2,030 infertility patients with PCOS underwent the follicular phase long-acting long protocol IVF/ICSI in the reproductive medicine center from January 2017 to December 2019. Intervention(s) None. Main outcome measure(s) Logistic regression analysis was used to analyze the factors associated with a high risk of OHSS. We established a nomogram to predict the risk of OHSS in infertility patients with PCOS after oocyte retrieval. Result(s) The incidence of patients at high risk of OHSS was significantly different from season-to-season and was especially higher in the summer and winter. Multivariate logistic analysis showed that gonadotropin dosage, number of retrieved oocytes, estradiol level, average bilateral ovarian diameter on the day human chorionic gonadotropin was administered, type of infertility, and average temperature were independent risk factors for OHSS after oocyte retrieval in PCOS patients. Based on the above independent risk factors, we constructed a prediction model for OHSS risk. To evaluate the efficiency of the prediction model, we calculated the C-index (0.849), area under the receiver operating characteristic curve (0.849), and internal validation C-index (0.846). Decision curve analysis suggested that the prediction model exhibited significant net benefits. Conclusion(s) The incidence of PCOS patients at high risk for OHSS after oocyte retrieval fluctuated with seasonal temperature changes, and was significantly higher in extreme climates. The prediction model had favorable predictive performance and clinical application value.
Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain

The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer’s disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables. Cingulate gyrus was obtained from AD cases and controls, from three brain banks. Gas chromatography-mass spectrometry (GC-MS) was used to measure and compare the levels of 66 identifiable metabolites in these tissues to determine effects of tissue-collection variables. The effect of PMD was further investigated by analysis of rat brain cortex and cerebellum collected following post-mortem delays (PMDs) of zero to 72 h. Metabolite levels between cases and controls were not replicable across cohorts with variable age- and gender-matching, PMD, and control Braak staging. Analysis of rat tissues found significant effects of PMD on 31 of 63 identified metabolites over periods up to 72 h. PMD must be kept under 24 h for metabolomics analyses on brain tissues to yield replicable results. Tissues should also be well age- and gender-matched, and Braak stage in controls should be kept to a minimum in order to minimize the impact of these variables in influencing metabolite variability.
Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma

Simple Summary Thyroid cancer incidence is increasing, with overdiagnosis being the major driver of the thyroid cancer “epidemic”. Papillary thyroid carcinoma, usually with excellent prognosis, sometimes has an aggressive metastatic pattern. This heterogeneity in progression makes it difficult to tailor treatment strategies for an individual patient. We aimed to identify clinicopathological factors associated with papillary thyroid carcinoma recurrence, persistence, and specific mortality. Our study supports that both pre-surgical factors, such as male gender, presence of psammoma bodies, gross extra-thyroidal extension, and lateral compartment lymph node metastases, as well as lymph vessel invasion, venous invasion, presence of necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of PTC patients. The same is true when analysis is restricted to stage I patients. The importance of this report is to emphasize clinical and imaging pre-surgical thyroid cancer patients’ evaluation for an appropriate surgical treatment and patient prognosis. Abstract Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.
Embedding Ordered Mesoporous Carbons into Thermosensitive Hydrogels: A Cutting-Edge Strategy to Vehiculate a Cargo and Control Its Release Profile

The high drug loading capacity, cytocompatibility and easy functionalization of ordered mesoporous carbons (OMCs) make them attractive nanocarriers to treat several pathologies. OMCs’ efficiency could be further increased by embedding them into a hydrogel phase for an in loco prolonged drug release. In this work, OMCs were embedded into injectable thermosensitive hydrogels. In detail, rod-like (diameter ca. 250 nm, length ca. 700 nm) and spherical (diameter approximately 120 nm) OMCs were synthesized by nanocasting selected templates and loaded with ibuprofen through a melt infiltration method to achieve complete filling of their pores (100% loading yield). In parallel, an amphiphilic Poloxamer® 407-based poly(ether urethane) was synthesized (Mn¯ 72 kDa) and solubilized at 15 and 20% w/v concentration in saline solution to design thermosensitive hydrogels. OMC incorporation into the hydrogels (10 mg/mL concentration) did not negatively affect their gelation potential. Hybrid systems successfully released ibuprofen at a slower rate compared to control gels (gels embedding ibuprofen as such), but with no significant differences between rod-like and spherical OMC-loaded gels. OMCs can thus work as effective drug reservoirs that progressively release their payload over time and also upon encapsulation in a hydrogel phase, thus opening the way to their application to treat many different pathological states (e.g., as topical medications).
Recent Advances Regarding the Phytochemical and Therapeutic Uses of Populus nigra L. Buds

Populus nigra L. (Salicaceae family) is one of the most popular trees that can be found in deciduous forests. Some particularities that characterize the Populus genus refer to the fact that it includes more than 40 species, being widespread especially in Europe and Asia. Many residues, parts of this tree can be used as a bioresource for different extracts as active ingredients in pharmaceuticals next to multiple benefits in many areas of medicine. The present review discusses the latest findings regarding the phytochemical composition and the therapeutic properties of Populus nigra L. buds. The vegetal product has been described mainly to contain phenolic compounds (phenols, phenolic acids and phenylpropanoids), terpenoids (mono and sesquiterpenoids), flavones (e.g., apigenol and crysin), flavanones (e.g., pinocembrin and pinostrombin), caffeic/ferulic acids and their derivates, and more than 48 phytocompounds in the essential oils. The resinous exudates present on the buds have been the major plant source used by bees to form propolis. Several studies depicted its antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, antitumor, hepatoprotective, hypouricemic properties and its effects on melanin production. All these lead to the conclusion that black poplar buds are a valuable and important source of bioactive compounds responsible for a wide range of therapeutic uses, being a promising candidate as a complementary and/or alternative source for a large number of health problems. The aim of the review is to gather the existing information and to bring an up to date regarding the phytochemical and therapeutic uses of Populus nigra L. buds.
High‐risk human papilloma virus was not detected in a Norwegian cohort of oral squamous cell carcinoma of the mobile tongue

The presence of and the causative role of high‐risk human papilloma virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The disagreement can be related to the misclassification of OSCC as oropharyngeal squamous cell carcinoma and/or lack of standard detection methods. This study aimed to examine the presence of transcriptionally active high‐risk HPV in a homogenous Norwegian cohort of primary and second primary OSCC of the mobile tongue (oral tongue squamous cell carcinoma—OTSCC).
White matter integrity correlates with cognition and disease severity in Fabry disease.

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.
Acid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections

Previous studies have shown that sphingosine kills a variety of pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. Sphingosine concentrations are decreased in airway epithelial cells of cystic fibrosis (CF) mice, and this defect has been linked to the infection susceptibility of these mice. Here, we tested whether the genetic overexpression of acid ceramidase rescues cystic fibrosis mice from pulmonary infections with P. aeruginosa. ABSTRACT Previous studies have shown that sphingosine kills a variety of pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. Sphingosine concentrations are decreased in airway epithelial cells of cystic fibrosis (CF) mice, and this defect has been linked to the infection susceptibility of these mice. Here, we tested whether the genetic overexpression of acid ceramidase rescues cystic fibrosis mice from pulmonary infections with P. aeruginosa. We demonstrate that the transgenic overexpression of acid ceramidase in CF mice corresponds to the overexpression of acid ceramidase in bronchial and tracheal epithelial cells and normalizes ceramide and sphingosine levels in bronchial and tracheal epithelial cells. In addition, the expression of β1-integrin, which is ectopically expressed on the luminal surface of airway epithelial cells in cystic fibrosis mice, an alteration that is very important for mediating pulmonary P. aeruginosa infections in cystic fibrosis, is normalized in cystic fibrosis airways upon the overexpression of acid ceramidase. Most importantly, the overexpression of acid ceramidase protects cystic fibrosis mice from pulmonary P. aeruginosa infections. Infection of CF mice or CF mice that inhaled sphingosine with P. aeruginosa or a P. aeruginosa mutant that is resistant to sphingosine indicates that sphingosine and not a metabolite kills P. aeruginosa upon pulmonary infection. These studies further support the use of acid ceramidase and its metabolite sphingosine as potential treatments of cystic fibrosis.
Allostatic Load in Cancer: A Systematic Review and Mini Meta-Analysis

Background: Individuals with cancer experience stress throughout the cancer trajectory. Allostatic load (AL), a cumulative multi-system measure, may have a greater value in stress assessment and the associated biological burden than individual biomarkers. A better understanding of the use of AL and its operationalization in cancer could aid in early detection and prevention or alleviation of AL in this population. Purpose: To consolidate findings on the operationalization, antecedents, and outcomes of AL in cancer. Methods: Seven databases (CINAHL, Ovid MEDLINE, Web of Science, APA PsycInfo, Scopus, Embase, and Cochrane CENTRAL) were searched for articles published through April 2020. The NIH tools were used to assess study quality. Results: Twelve studies met inclusion criteria for this review. Although variability existed in the estimation of AL, biomarkers of cardiovascular, metabolic, and immune systems were mostly used. Associations of AL with cancer-specific variables were examined mostly utilizing population-databases. Significant associations of AL with variables such as cancer-related stress, positive cancer history, post traumatic growth, resilience, tumor pathology, and cancer-specific mortality were found. Mini meta-analysis found that a one-unit increase in AL was associated with a 9% increased risk of cancer-specific mortality. Conclusion: This review reveals heterogeneity in operationalization of AL in cancer research and lack of clarity regarding causal direction between AL and cancer. Nevertheless, AL holds a significant promise in cancer research and practice. AL could be included as a screening tool for high-risk individuals or a health outcome in cancer. Optimal standardized approaches to measure AL would improve its clinical utility.
Blood-brain barrier permeability analysis of plant ceramides

Ceramides, a type of sphingolipid, are cell membrane components and lipid mediators that modulate a variety of cell functions. In plants, ceramides are mostly present in a glucosylated glucosylceramide (GlcCer) form. We previously showed that oral administration of konjac-derived GlcCer to a mouse model of Alzheimer’s disease reduced brain amyloid-β and amyloid plaques. Dietary plant GlcCer compounds are absorbed as ceramides, but it is unclear whether they can cross the blood-brain barrier (BBB). Herein, we evaluated the BBB permeability of synthetic plant-type ceramides (4, 8-sphingadienine, d18:2) using mouse and BBB cell culture models, and found that they could permeate the BBB both in vivo and in vitro. In addition, administrated ceramides were partially metabolized to other sphingolipid species, namely sphingomyelin (SM) and GlcCer, while crossing the BBB. Thus, plant ceramides can cross the BBB, suggesting that ceramides and their metabolites might affect brain functions.