Significant Reduction Research Articles

Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242). CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.

Tomographic task solution using a dichotomous discretization scheme in polar coordinates and partial system matrices invariant to rotations

Objectives. The purpose of this work was to create an effective iterative algorithm for the tomographic reconstruction of objects with large volumes of initial data. Unlike the convolutional projection algorithm, widely used in commercial industrial and medical tomographic devices, algebraic iterative reconstruction methods use significant amounts of memory and typically involve long reconstruction times. At the same time, iterative methods enable a wider range of diagnostic tasks to be resolved where greater accuracy of reconstruction is required, as well as in cases where a limited amount of data is used for sparse-view angle shooting or shooting with a limited angular range.Methods. A feature of the algorithm thus created is the use of a polar coordinate system in which the projection system matrices are invariant with respect to the rotation of the object. This enables a signification reduction of the amount of memory required for system matrices storage and the use of graphics processors for reconstruction. Unlike the simple polar coordinate system used earlier, we used a coordinate system with a dichotomous division of the reconstruction field enabling us to ensure invariance to rotations and at the same time a fairly uniform distribution of spatial resolution over the reconstruction field.Results. A reconstruction algorithm was developed on the basis of the use of partial system matrices corresponding to the dichotomous division of the image field into partial annular reconstruction regions. A 2D and 3D digital phantom was used to show the features of the proposed reconstruction algorithm and its applicability to solving tomographic problems.Conclusions. The proposed algorithm allows algebraic image reconstruction to be implemented using standard libraries for working with sparse matrices based on desktop computers with graphics processors.

Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF.

Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders. This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation. Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect. Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05). Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.

Evaluation of an automated platelet aggregation method for detection of congenital or acquired platelet function defects.

Light transmission aggregometry (LTA) is the most widely used laboratory method for an initial screening of patients with a suspected platelet function defect (PFD), and its use has also been proposed for assessing the efficacy of antiplatelet treatment (APT). An automated LTA method has been developed by Sysmex (Kobe, Japan) on a routine coagulation analyzer (CS-2400), together with a new research parameter called PAL (platelet aggregation level) to evaluate patients on APT. We evaluated the performance of CS-2400 compared to a stand-alone lumi-dual-aggregometer device in the diagnosis of PFD and in assessing the efficacy of APT. For these purposes, the study population was represented by a cohort of 23 patients with a previous diagnosis of PFD and a cohort of 28 patients on APT. Compared to healthy volunteers, patients with PFD showed a statistically significant reduction (p<0.05) in the maximal %light transmission, irrespective of the agonist used, both with the CS-2400 and the lumi-dual-aggregometer. As regards PFD patients, CS-2400 was effective in identifying the more severe defects, with a good sensibility and specificity, but less effective in identifying milder forms of PFD, such as platelet secretion defects. Patients on APT showed a statistically significant (p=0.001) reduced median %light transmission and PAL scores compared to healthy controls. Thanks to this LTA technology, CS-2400, a routine coagulation analyzer widely available in routine laboratories, could prove useful for initial assessment of patients with a suspected PFD. Moreover, the PAL scores were a fairly accurate reflection of the platelet response to APT.

CD44 facilitates adhesive interactions in airineme-mediated intercellular signaling.

Specialized cellular protrusions facilitate local intercellular communications in various species, including mammals. Among these, airinemes play a crucial role in pigment pattern formation in zebrafish by mediating long-distance Notch signaling between pigment cells. Remarkably, airinemes exhibit large vesicle-like structure at their tips, which are pulled by a macrophage subpopulation and delivered to target cells. The interaction between macrophages and Delta-ligand carrying airineme vesicles is essential for initiating airineme-mediated signaling, yet the molecular detail of this interaction remains elusive. Through high-resolution live imaging and genetic in vivo manipulations, we found that adhesive interactions via the extracellular domain of CD44, a class I transmembrane glycoprotein, between macrophages and airineme vesicles are critical for airineme signaling. Mutants lacking the extracellular domain of CD44 lose their adhesiveness, resulting in a significant reduction in airineme extension and pigment pattern defects. Our findings provide valuable insights into the role of adhesive interactions between signal-sending cells and macrophages in a long-range intercellular signaling.

Assessment of the Efficacy and Durability of IncobotulinumtoxinA in the Treatment of the Upper Face in Adult Women.

IncobotulinumtoxinA (Xeomin®) is used in the treatment of dynamic wrinkles and the aesthetic repositioning of facial structures. The duration of its muscular effect typically extends for around 4months. However, the residual aesthetic benefit can be observed for a longer period. To date, the long-term aesthetic benefit of incobotulinumtoxinA in facial aesthetics has not been systematically evaluated. This study aimed to evaluate longitudinally the duration and aesthetic benefits of incobotulinumtoxinA in the treatment of the upper face in adult women. A quasi-experimental, evaluator-blind, clinical trial involving 28 adult women (30-60years old) with facial movement lines, undergoing treatment of the upper face with incobotulinumtoxinA by two injectors, following an individualized protocol (ONE21 and glabellar contraction patterns) was performed. Participants were evaluated on the day of the intervention (day0) and days30, 120, 180, and 240, and subjected to standardized photographs. The following outcomes were evaluated blindly at each visit: Merz Aesthetics Facial Contraction Scale (MAS), GAIS (Global Aesthetic Improvement Scale), and patient satisfaction. Adverse effects were evaluated at each visit. Participants ranged in age from 30 to 60years, 93% were self-declared white, and most of their baseline MAS scores for dynamic lines were moderate and severe. All the parameters presented significative reduction from baseline until day180. At day240, the dynamic MAS scores were lower than baseline for forehead lines in 15.4% (95% confidence interval (CI) 0.8-30.0%) of the participants, for glabellar lines in 38.5% (95%CI 18.8-58.1%), and for crow's feet lines in 26.9% (95%CI 9.0-44.8%). Aesthetic improvement compared to baseline was identified in 35% (CI 95% 23‒50%) of the participants at day240, and 62% (CI 95% 42‒81%) of the sample kept reporting some satisfaction with the procedure. The aesthetic treatment of the upper face with incobotulinumtoxinA demonstrates enduring clinical benefits, and patient satisfaction lasting up to 180days in most participants. The length of efficacy, which exceeded those reported in the literature, may be attributed to the use of techniques based on individualized assessment such as ONE21 and glabellar patterns of contraction.

A Blockchain-Based Model for Traceability and Quality Management of Raw Materials in Clothing Products

In this study, we employ blockchain-based traceability technology to construct a comprehensive model for raw material traceability and quality management in clothing products. Additionally, we investigate engineered water nanostructures (EWNS) for their antibacterial, hydrophilic, and anti-pilling effects on textiles. The EWNS can serve as an effective tool for monitoring quality, enabling precise tracking and verification of nanomaterials during clothing production. The research validated the traceability performance of the blockchain-based model for raw material traceability and quality management in clothing products, achieving a remarkable traceability accuracy of 99.92% and an exceptionally low traceability response time of merely 1.83 seconds. Moreover, after being treated with EWNS, antibacterial rates against E. coli and S. aureus in clothing antibacterial quality management reached 99.9% and 99.0%, respectively. In the hydrophilicity test, EWNS was applied to clothing for a duration of 1 to 7 hours, resulting in a significant reduction in the wetting time of clothing from 10.8 seconds to 1.2 seconds. In the anti-pilling tests, there was a notable enhancement in the effectiveness of anti-pilling properties after EWNS treatment. In summary, our model has achieved remarkable outcomes in material traceability and quality management, offering consumers and the clothing industry a reliable method to ensure product quality and traceability, while simultaneously improving performance aspects such as antibacterial efficacy, hydrophilicity, and resistance against pilling.

N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions. This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues. The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis. The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes. The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

Analytic Prediction of Rotor Broadband Noise with Serrated Trailing Edges with Applications to Urban Air Mobility Aircraft

Theoretical predictions for broadband noise generated by rotors with serrated trailing edges are presented. This study extends Lyu and Ayton’s model for serrated trailing-edge noise to account for factors such as finite span length, the accurate acoustic attenuation rate of trailing-edge noise, modified spanwise wavenumber, and the proper scattering factor. This new model is implemented in the rotorcraft broadband noise tool, UCD‐QuietFly. The validation results demonstrate a satisfactory level of agreement with the experimental data for serrated trailing‐edge noise of a wing section, a hovering rotor, and a forward‐flight rotor. Next, the effects of serration parameters, such as the number of serrations, serrations starting radial location, serration geometry, and serration height, on rotor broadband noise are investigated. For example, it is observed that sine-wave, chopped peak, or sawtooth serration shapes provide the most significant noise reduction among the various shapes considered. Finally, broadband noise reduction through serrations is applied to two urban air mobility aircraft scenarios: a six‐passenger quadrotor and a quiet helicopter. For the quadrotor, serrated trailing edges show a noise reduction potential of over 9 dB, with higher reductions observed at higher tip speeds and fewer blades. A quiet helicopter equipped with serrated blades in forward flight achieves a maximum noise reduction of over 10 dB in the forward direction.

Exploring the antinociceptive potential of homoeriodictyol in nociception models

Context: Homoeriodictyol is a flavonoid with known antioxidant, anti-inflammatory, and anti-tumor properties found in various plants. However, its potential analgesic effects have not been explored. Aims: To investigate the pain-relieving properties of homoeriodictyol using different mouse models of nociception. Methods: Various doses of homoeriodictyol (50, 100, 150, and 200 µg/kg) were administered to mice and evaluated using the acetic acid-induced writhing test, the hot plate test, and the formalin-induced paw licking assay. These effects were compared with those of mice treated with acetylsalicylic acid or morphine, both with and without naloxone, an opioid receptor antagonist. Additionally, capsaicin- and glutamate-induced paw-licking tests were conducted to assess the involvement of the vanilloid and glutamatergic systems, respectively. Results: Homoeriodictyol demonstrated a significant and dose-dependent reduction in nociceptive behavior in the acetic acid-induced writhing test, achieving a 52.4% inhibition at a dose of 200 µg/kg. It also substantially increased the latency period in response to the hot plate test (65.8% at 200 µg/kg) and significantly suppressed both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Notably, the effects of homoeriodictyol in the hot plate test and formalin-induced paw-licking test were significantly reversed by naloxone. Furthermore, homoeriodictyol effectively reduced neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57.8% and 76.9%, respectively, at a dose of 200 µg/kg). Conclusions: This study concludes that homoeriodictyol exhibits antinociceptive activity in mice, acting through both central and peripheral pathways.

Evaluation of the Therapeutic Effect of Preventive External Application of Traditional Chinese Medicine Gel Combined with Psychological Care in Tumor Patients with Radiation Dermatitis

Radiation dermatitis (RD) caused by radiation therapy has brought pain to patients. Therefore, we aim to investigate the efficacy of preventive external application of Traditional Chinese medicine (TCM) gel in conjunction with psychological care for the prevention of RD in patients with malignant tumors. A total of 130 patients who underwent radiotherapy in our hospital from January 2021 to December 2022 were selected as the research objects. The patients were divided into two groups based on their nursing modes: the conventional group received TCM gel treatment for Radiation Therapy Oncology Group (RTOG) grade II skin damage, while the combination group received preventive external application of TCM gel before radiotherapy along with psychological care support. The incidence of RD, quality of life, negative emotional changes, and satisfaction with nursing care were recorded and compared between the two groups. Our results demonstrated a significant reduction in the incidence of RTOG grade III–IV skin damage, an obvious improvement in patient’s quality of life and negative emotions, and a higher satisfaction in the combination group compared to the conventional group (P &lt; 0.05). In conclusion, this study suggests that the preventive external application of traditional Chinese medicine combined with psychological care during radiotherapy holds significant potential in preventing RD in patients with malignant tumors. Furthermore, it is proposed that the observed efficacy of the Chinese medicine gel in preventing radiation dermatitis may be attributed to its anti-inflammatory properties, primarily mediated by key active ingredients such as berberine and obacunone.

Mesenchymal Stem Cell-Derived Exosomes Mitigate Acute Murine Liver Injury via Ets-1 and Heme Oxygenase-1 Up-regulation.

Mesenchymal stem cells (MSCs)-derived exosomes have been previously demonstrated to promote tissue regeneration in various animal disease models. This study investigated the protective effect of exosome treatment in carbon tetrachloride (CCl4)-induced acute liver injury and delineated possible underlying mechanism. Exosomes collected from conditioned media of previously characterized human umbilical cord-derived MSCs were intravenously administered into male CD-1 mice with CCl4-induced acute liver injury. Biochemical, histological and molecular parameters were used to evaluate the severity of liver injury. A rat hepatocyte cell line, Clone-9, was used to validate the molecular changes by exosome treatment. Exosome treatment significantly suppressed plasma levels of AST, ALT, and pro-inflammatory cytokines, including IL-6 and TNF-α, in the mice with CCl4-induced acute liver injury. Histological morphometry revealed a significant reduction in the necropoptic area in the injured livers following exosome therapy. Consistently, western blot analysis indicated marked elevations in hepatic expression of PCNA, c-Met, Ets-1, and HO-1 proteins after exosome treatment. Besides, the phosphorylation level of signaling mediator JNK was significantly increased, and that of p38 was restored by exosome therapy. Immunohistochemistry double staining confirmed nuclear Ets-1 expression and cytoplasmic localization of c-Met and HO-1 proteins. In vitro studies demonstrated that exosome treatment increased the proliferation of Clone-9 hepatocytes and protected them from CCl4-induced cytotoxicity. Kinase inhibition experiment indicated that the exosome-driven hepatoprotection might be mediated through the JNK pathway. Exosome therapy activates the JNK signaling activation pathway as well as up-regulates Ets-1 and HO-1 expression, thereby protecting hepatocytes against hepatotoxin-induced cell death.

Practice-based evidence for spiritually integrated psychotherapies: Examining trajectories of psychological and spiritual distress.

The aims of this practice-based evidence study were to (a) examine clients' trajectories of psychological and spiritual distress over the course of spiritually integrated psychotherapies (SIPs) and (b) explore the role of varying types of spiritual interventions in these outcomes. In total, 164 practitioners of SIPs from 37 settings in a practice-research network administered the Clinically Adaptive Multidimensional Outcome Survey (Sanders et al., 2018) at each session with 1,227 clients and reported their use of theoretical orientations and spiritual interventions on an after-session summary checklist. Focusing on sessions over an initial 12-week period, latent growth curve modeling analyses revealed that clients, on average, experienced significant reduction of psychological distress during their engagement in SIPs with improvements occurring most sharply in the first month. Further, other findings revealed a salient reciprocal interplay with spiritual distress throughout treatment, such that clients who were struggling with their religious faith and/or spirituality were more psychologically distressed and displayed a more attenuated and gradual pattern of symptom reduction. In such cases, clinicians frequently utilized spiritual interventions involving basic skills (e.g., spiritual assessment), virtues (e.g., discuss self-control), and religious attachment (e.g., encourage acceptance of divine love) that were uniquely associated with clients' rate and duration of decline in psychological and spiritual distress. The present findings affirm the routine effectiveness of SIPs along with highlighting the potential value of certain spiritual interventions in supporting holistic recovery among clients who want clinicians to be culturally responsive to their spiritual and/or religious identities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cardiovascular Protection of Aspirin in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

This is to evaluate aspirin's cardiovascular (CV) protective effect in chronic kidney disease (CKD) patients. We searched PubMed, Embase, Cochrane Library, and Web of Science (up to December 2022) for randomized controlled trials (RCTs) and observational studies comparing aspirin with placebo in CKD patients for the prevention of CV disease (CVD). Efficacy outcomes included CVD, heart failure, myocardial infarction, stroke, CV and all-cause mortality; safety outcomes included major bleeding, minor bleeding, and renal events. Six RCTs and 6 observational studies, including 35,640 participants, met the inclusion criteria and reported relevant CV outcomes, with a mean follow-up of 46.83 months. The pooled data showed aspirin had no significant preventive effect on CVD events (RR=1.03; 95% CI, 0.84-1.27). However, CV mortality was significantly reduced in the aspirin group (RR=0.74; 95% CI, 0.58-0.95). Furthermore, aspirin use did not increase the risk of major bleeding and renal events but significantly increased minor bleeding events (RR=2.11; 95% CI, 1.30-3.44). Renal events were significantly increased after sensitivity analysis (RR=1.10; 95% CI, 1.04-1.16). Aspirin did not prevent CV events, with a significantly increased risk of minor bleeding and renal events. Besides, aspirin use had no statistically significant reduction in the risk of all-cause mortality but had a statistically significant reduction in the risk of CV mortality.

Influence of propiconazole and metconazole formulations on Bacillus subtilis vegetative cell growth and disease control of fruit crops.

Biological control agent (BCA) Bacillus subtilis formulated as Theia® is registered for control of fungal and bacterial diseases of fruit crops. Combinations of Theia® and strategic concentrations of two demethylation inhibitor (DMI) fungicides were investigated to explore potential synergisms. Bacteria were cultured in nutrient broth and combined with technical grades and two formulations of propiconazole (EC and WP) and metconazole (EC and WDG) at 0, 10, 50, 100, and 150 µg/ml active ingredient. After co-cultivation, optical density (OD600) and colony forming units (CFU/ml) were evaluated. In contrast to EC formulations, the WP or WDG formulations at 10 or 50 µg/ml of both DMIs did not affect vegetative cell growth. The mixture of Theia® and each formulated DMI at 50 µg/ml active ingredient resulted in a significant reduction of Monilinia fructicola lesion development on apple, Colletotrichum siamense lesion development on cherry, and Botrytis cinerea lesion development on cherry. The combination of Theia® with EC formulations showed weaker disease reduction due to antagonism. Only Theia® + non-EC formulated propiconazole and metconazole significantly reduced brown rot disease incidence of apple compared to the respective solo treatments and anthracnose disease incidence of cherry compared to the untreated control. Our results indicated that at least some DMI fungicides possess bactericidal effects depending on the formulation and concentration. The combination of Theia® with a lower than label rate concentration (50 µg/ml) of the DMI fungicides propiconazole and metconazole showed potential for synergistic effects especially when non-EC formulations were used.

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.

The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. 47 BC Italian patients and healthy individuals (39 females and 66 males/ females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A- 158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

Region-Specific Decellularization of Porcine Uterine Tube Extracellular Matrix: A New Approach for Reproductive Tissue-Engineering Applications.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Chloromonas rubrosalmonea sp. nov. (Chlorophyta) causes blooms of salmon-red snow due to high astaxanthin and low chlorophyll content

ABSTRACT Melting snowfields support microbial communities, including blooms of phototrophic psychrophiles. “Watermelon snow” and its flagship species Sanguina nivaloides are mostly found at exposed, alpine or polar sites. Here, we investigated an alga that is morphologically similar but likely less common, thriving in exposed or semi-exposed snowpacks at lower altitudes frequently close to the tree line, and causing characteristic, intensely salmon-red snow surface spots in Central European and Norwegian mountains. Our aim was to illustrate the taxonomic heterogeneity of red snow by performing a cellular and molecular characterization of this species. The phylogenetic analysis placed the alga into the genus Chloromonas, clade “group C”. Single-cell Sanger sequencing enabled us to link the cell morphotype to its genotype. In addition to light microscopy of the snow samples, applying 18S rRNA gene and ITS2 metabarcoding confirmed that this alga dominated the bloom communities. The cysts had multi-layered smooth cell walls, and had a broadly oval to fully spherical shape, in striking contrast to most other Chloromonas species found on snow surfaces. Another remarkable feature was a pronounced astaxanthin accumulation in relation to a low proportion of chlorophylls, occasionally accompanied by a significant reduction of thylakoid membranes. This likely caused the photosynthetic dormancy of mature cysts found in some samples. Based on these data, we describe the snow alga as Chloromonas rubrosalmonea, sp. nov.

Impact of refresher training on the outcomes of trachomatous trichiasis surgery

Background/aimsTrachomatous trichiasis (TT) is a severe consequence of chronic inflammation/conjunctival scarring resulting from trachoma, the leading infectious cause of blindness worldwide. Our prospective cohort study evaluated the effectiveness of refresher...

Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-HER2 scFvs.

We aimed to assess the effects of a cocktail comprising three specific anti- HER2 scFvs on breast tumor formation in a xenograft mouse model and to evaluate quantitative changes in the tumor using stereological analysis. Three specific anti-HER2 phage antibodies were produced from a scFv-library using phage display technology. The cell binding capacities of the antibodies were assessed via FACS analysis. Soluble forms of the antibodies were prepared by infecting HB2151-E. coli cells and purified using a centrifugal ultrafiltration method. The purification process was evaluated by SDSPAGE analysis. Two forms of scFv cocktails were prepared, soluble scFv and phage-scFv cocktail, which contained an equal amount/phage of each of the three antibodies. Inbred female BALB/c mice were pretreated with 5 and 20 mg/kg of the soluble scFv cocktail and 1011 phage-scFv cocktail/ kg. The mice were then injected with 2×106 SKBR-3 human breast cancer cells. Total tumor, inflammatory and non-inflammatory volumes were estimated using the Cavalieri principle after preparing photomicrograph slides. The anti-HER2 scFvs showed significantly higher binding to SKBR-3 cells compared to the isotype control. SDS-PAGE analysis confirmed the high purification of the scFvs. Stereological analysis revealed that the group pretreated with 20 mg/kg of the soluble scFv cocktail exhibited the highest reductions in total tumor volume, non-inflammatory volume, and inflammatory volume, with reductions of 73%, 78%, and 72%, respectively, compared to PBS-pretreated mice (P-value < 0.0001). The volumetric ratio of necrotic tissue to total tumor volume increased by 2.2-fold and 2- fold in the 20 mg/kg of soluble scFv cocktail and phage-scFv cocktail groups, respectively, compared to the PBS-treated mice (P-value < 0.05). Pre-treatment with a 20 mg/kg anti-HER2 scFv cocktail resulted in a significant reduction in tumor volume and increased necrotic area in a human breast cancer xenograft model, indicating the remarkable anti-tumor effect of the cocktail in vivo.