Neutrophil phenotypic characteristics in children with congenital asplenia and splenectomized for hereditary spherocytosis

The spleen plays an important role in the granulocyte homeostasis due to such mechanisms as pooling, elimination of senescent cells and regulatory effects on granulocyte renewal in the bone marrow. The expression profile of granulocyte receptors was tested in children with congenital asplenia, and splenectomized for spherocytosis. Receptors tested included those appearing with maturation (CD16, CD11b, CD11c, TREM-1), disappearing (CD54, CD49d, CD64) and maintained during maturation (CD11a, CD45). In general, we found that the circulating granulocyte pool in the asplenic patients had phenotypical features of highly matured but not apoptotic neutrophils with a significantly elevated expression of CD16 (CD16(high)), tendency to a lower expression of CD45 (CD45(low)) and an unchanged expression of CD64 (and other markers indicating systemic inflammatory reactions). The high fluorescence intensity of CD11b,c, and TREM-1 in the congenital asplenia may indicate a potentially elevated pro-inflammatory status of granulocytes, possibly due to the low activity of vagus nerve and spleen-dependent cholinergic anti-inflammatory pathway.     

Surface Modification of Nanocrystalline LiMn2O4 Using Graphene Oxide Flakes

In this work, a facile, wet chemical synthesis was utilized to achieve a series of lithium manganese oxide (LiMn₂O₄, (LMO) with 1–5%wt. graphene oxide (GO) composites. The average crystallite sizes estimated by the Rietveld method of LMO/GO nanocomposites were in the range of 18–27 nm. The electrochemical performance was studied using CR2013 coin-type cell batteries prepared from pristine LMO material and LMO modified with 5%wt. GO. Synthesized materials were tested as positive electrodes for Li-ion batteries in the voltage range between 3.0 and 4.3 V at room temperature. The specific discharge capacity after 100 cycles for LMO and LMO/5%wt. GO were 84 and 83 mAh g⁻¹, respectively. The LMO material modified with 5%wt. of graphene oxide flakes retained more than 91% of its initial specific capacity, as compared with the 86% of pristine LMO material.     

Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

Viburnum opulus L.—A Review of Phytochemistry and Biological Effects

Viburnum opulus (VO) is a valuable decorative, medicinal, and food plant. This deciduous shrub is found in natural habitats in Europe, Russia, and some regions in North Africa and North Asia. The VO is traditionally used to treat aliments such as cough, colds, tuberculosis, rheumatic aches, ulcers, stomach, and kidney problems, among others. Many of the health-promoting properties of VO are associated with antioxidant activity, which has been demonstrated in both in vitro and in vivo studies. The results of in vitro studies show the antimicrobial potential of VO, especially against Gram-positive bacteria. In cell-based studies, VO demonstrated anti-inflammatory, anti-obesity, anti-diabetic, osteogenic, cardio-protective, and cytoprotective properties. The applicability of VO in the treatment of urinary tract diseases, endometriosis, and some cancers has been confirmed in in vivo studies. The health benefits of VO result from the presence of bioactive components such as phenolic compounds, vitamin C, carotenoids, iridoids, and essential oils. The aim of this review is to present an overview of the botanical characteristics, chemical compositions, including bioactive compounds, and pro-health properties of VO different morphological parts.     

Gentamicin-Loaded Polysaccharide Membranes for Prevention and Treatment of Post-operative Wound Infections in the Skeletal System

Purpose

To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections.

Methods

Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed.

Results

The most appropriate handling and mechanical properties (Young’s modulus, E = 92 ± 4 MPa and breaking force, F _MAX  = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F _MAX  = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced.

Conclusions

GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.

     

Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study

1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain.

2. The time-dependent distribution was investigated after an i.p. dose of 25?mg/kg at 0, 5, 30, 120, 240, 360 and 480?min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte.

3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (C_max) of 1034.9?ng/mL at 240?min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5?min and its slow elimination after 360-min postdose.

4. Our findings confirm that MALDI MSI provides an advanced, label-free and faster alternative technique for xenobiotic distribution such as DOX in tissues, making it an essential drug discovery tool for other possible neuroprotective agents.     

Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

Alternaria toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent Alternaria mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor β (ERβ) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor β (ERβ) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERβ, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.     

High Fat,High Sugar Diet and DJOS Bariatric Surgery Influence Plasma Levels of Fetuin-B,Growth Differentiation Factor-15, and Pentraxin 3 in Diet-Induced Obese Sprague–Dawley Rats

The liver plays a central role in glucose and fatty acid metabolism and acts as an endocrine organ that secretes hepatokines with diverse systemic effects. The study aimed to examine the influence of duodenojejunal omega switch (DJOS) bariatric surgery in combination with different diets on glucose administration parameters and hepatokines levels. After 8 weeks on high fat, high sugar diet (HFS) or control diets (CD), Sprague–Dawley rats underwent DJOS or SHAM (control) surgery. For the next 8 weeks after the surgery, half of DJOS and SHAM-operated animals were kept on the same diet as before, and half had a diet change. The oral glucose tolerance test (OGTT) was performed three times: 8 weeks before and 4 and 8 weeks after surgery. Fetuin-B, growth differentiation factor-15 (GDF-15), pentraxin 3 (PTX3) plasma levels were analyzed. DJOS surgery had a beneficial effect on oral glucose tolerance test (OGTT) results and the area under the curve (AUC_OGTT). The OGTT results depended on the time elapsed after the surgery, the type of diet used, the surgery performed, and the interaction between these factors. DJOS bariatric surgery reduced fetuin-B and GDF15 plasma levels. Interaction between the type of surgery performed and diet used influenced the fetuin-B and PTX-3 plasma levels. A dietary regime is essential to achieve therapeutic and clinical goals after bariatric surgery.     

Vitamin D Supplementation and Mental Health in Multiple Sclerosis Patients: A Systematic Review

Vitamin D has a promising role in multiple sclerosis (MS) management, and it has been found to be beneficial for patients’ mental health, which is reduced in MS patients. The aim of the present study was to conduct a systematic review of the literature to assess the influence of vitamin D supplementation on mental health in MS patients. The systematic review was registered in the PROSPERO database (CRD42020155779) and it was conducted on the basis of the PRISMA guidelines. The search procedure was conducted using PubMed and Web of Science databases and it included studies published up until September 2021. Six studies were included in the systematic review. The risk of bias was analyzed using the Newcastle–Ottawa Scale (NOS). Within the included studies, there were two studies randomized against placebo and four other prospective studies. The studies presented vitamin D interventions randomized against placebo or not randomized, while supplementation was applied for various durations—from 4 weeks to 12 months, or the studies compared patients who applied vitamin D supplementation and those who did not apply it and verified the effect of the supplementation after a number of years. The mental health outcomes that were assessed included quality of life, depression/depressive symptoms, and fatigue as an additional element. The majority of studies supported the positive influence of vitamin D on the mental health of MS patients, including the study characterized as having the highest quality (randomized against placebo with the highest NOS score). All the studies that assessed the quality of life indicated the positive influence of vitamin D while the studies that did not find a positive influence of vitamin D were conducted for depression/depressive symptoms. In spite of the fact that only a small number of studies have been conducted so far, and only two studies were randomized against a placebo, some conclusions may be formulated. The systematic review allowed us to conclude that there may be a positive effect of vitamin D supplementation in MS patients, which was stated in all of the studies analyzing quality of life, as well as in one study analyzing depressive symptoms. Considering that vitamin D deficiency is common in MS patients, and the potential positive influence of supplementation on the quality of life, supplementation should be applied at least in doses that cover the recommended intake.