Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Upon transmission to the human host, Plasmodium sporozoites exit the skin, are taken up by the blood stream, and then travel to the liver where they infect and significantly modify a single hepatocyte. Low infection rates within the liver have made proteomic studies of infected hepatocytes challenging, particularly in vivo, and existing studies have been largely unable to consider how protein and phosphoprotein differences are altered at different spatial locations within the heterogeneous liver. Using digital spatial profiling, we characterized changes in host signaling during Plasmodium yoelii infection in vivo without disrupting the liver tissue. Moreover, we measured alterations in protein expression around infected hepatocytes and identified a subset of CD163+ Kupffer cells that migrate towards infected cells during infection. These data offer the first insight into the heterogeneous microenvironment that surrounds the infected hepatocyte and provide insights into how the parasite may alter its milieu to influence its survival and modulate immunity.

Hemodialysis and Plasma Oxylipin Biotransformation in Peripheral Tissue

(1) Background: Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. (2) Methods: We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. (3) Results: Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. (4) Conclusions: The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.

Antimicrobial Resistance in Enterococci

Background. Enterococcus spp. are opportunistic agents of community-acquired and in-hospital infections, which have been considered a threat to public health due to their antimicrobial resistance, primarily to glycopeptides, in recent years.The aim of the study is to determine the prevalence of various Enterococcus species causing infections in hospitalized patients and their antimicrobial resistance.Methods included identification by MALDI-TOF mass spectrometry and antimicrobial susceptibility testing in accordance with the EUCAST or, in their absence, CLSI guidelines.Results. Antimicrobial resistance in 1562 consecutive Enterococcus strains isolated from hospitalized patients was determined in a major medical center admitting patients from various regions of the Russian Federation in 2019. The predominance of E.faecalis and E.faecium (99.5%) was revealed; the frequency of isolation of the former was 56% higher than that of the latter. E.avium, E.casseliflavus, E.gallinarum, E.durans were isolated from 0.5% of biological samples. The highest level of resistance of enterococci was observed to erythromycin (84.8%), tetracycline (75.0%), and rifampicin (68.2%). Multidrug, as well as vancomycin resistance, prevailed in E.faecium. All E.faecium strains isolated from blood were multidrug resistant. Resistance to vancomycin in enterococci, causing bloodstream infections, was observed solely in 19.5% of E.faecium; all vancomycin-resistant isolates were also resistant to teicoplanin. Linezolid resistance was detected in 2 community-acquired strains of E.faecalis (0.1%). Rare enterococci have shown diverse patterns of antimicrobial resistance.Conclusions. E.faecalis and E.faecium prevailed among Enterococcus spp. causing infections in hospitalized patients. Multidrug resistance and vancomycin resistance were observed predominantly in E.faecium, especially in strains causing blood-stream infections. Further monitoring of the spread and antimicrobial resistance of various Enterococcus spp. in hospital and community-acquired infections is needed.

Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved drug stability. One promising group of controlled and targeted drug delivery systems is polymer-based nanoparticles that can sustain the release of the active agent by diffusion and their degradation. Sorafenib is the only drug that can prolong the life of patients suffering from hepatocellular carcinoma. Cisplatin remains one of the most widely used broad-spectrum anticancer drugs for the treatment of a variety of solid tumours. Nanoformulations can exert a synergistic effect by entrapping two drugs with different modes of action, such as sorafenib and cisplatin. In our study, polymeric nanoparticles were prepared with a good production yield by an improved double emulsion solvent evaporation method using the copolymer of 12-hydroxystearic acid with ε-caprolactone (12CL), a biocatalytically synthesised biocompatible and biodegradable carrier, for the co-entrapment of sorafenib and cisplatin in nanotherapeutics. A bovine serum albumin (BSA) model compound was used to increase the cisplatin incorporation; then, it was successfully substituted by a iRGD tumour penetrating peptide that might provide a targeting function of the nanoparticles.

Targeted siRNA nanotherapeutics against breast and ovarian metastatic cancer: a comprehensive review of the literature

Metastasis is considered the major cause of unsuccessful cancer therapy. The metastatic development requires tumor cells to leave their initial site, circulate in the blood stream, acclimate to new cellular environments at a remote secondary site and endure there. There are several steps in metastasis, including invasion, intravasation, circulation, extravasation, premetastatic niche formation, micrometastasis and metastatic colonization. siRNA therapeutics are appreciated for their usefulness in treatment of cancer metastasis. However, siRNA therapy as a single therapy may not be a sufficient option for control of metastasis. By combining siRNA with targeting, functional agents or small molecule drugs have shown potential effects that enhance therapeutic effectiveness. This review addresses multidrug resistance and metastasis in breast and ovarian cancers and highlights drug delivery strategies using siRNA therapeutics.

Human Glucose Transporters in Renal Glucose Homeostasis

The kidney plays an important role in glucose homeostasis by releasing glucose into the blood stream to prevent hypoglycemia. It is also responsible for the filtration and subsequent reabsorption or excretion of glucose. As glucose is hydrophilic and soluble in water, it is unable to pass through the lipid bilayer on its own; therefore, transport takes place using carrier proteins localized to the plasma membrane. Both sodium-independent glucose transporters (GLUT proteins) and sodium-dependent glucose transporters (SGLT proteins) are expressed in kidney tissue, and mutations of the genes coding for these glucose transporters lead to renal disorders and diseases, including renal cancers. In addition, several diseases may disturb the expression and/or function of renal glucose transporters. The aim of this review is to describe the role of the kidney in glucose homeostasis and the contribution of glucose transporters in renal physiology and renal diseases.

Staphylococcus prettenkoferi – biochemical properties, methods of species identification and clinical significance

Staphylococcus pettenkoferi was first isolated from blood culture a 25-years-old patient with fever of unknown etiology. Based on the literature analysis, it was found that it is an opportunistic microorganism. It causes blood stream infections and was an causative agent of osteomyelitis. Staphylococcus pettenkoferi is a component of the human microbiome, was found in a hospital environment and was also isolated from animals and their surroundings.

Polymyxin B infusion related respiratory arrest: A case report

A 73 years old male, known hypertensive on medication, with the history of SARS-CoV-2 infection nine months ago, presented to us with mucormycosis, he was treated with Liposomal amphotericin B initially. He developed acute kidney injury with recurrent pulmonary oedema requiring ICU admission and Haemodialysis. He later developed catheter related blood stream infection that grew Carbapenem resistant Klebsiella pneumonia and was started on Polymyxin B. However from day 3 of antibiotics he started to develop recurrent respiratory arrest with no apparent cause. He required a brief period of mechanical ventilation and was successfully weaned. He had recurrent such episodes with no apparent cause. After extensive work up and literature search it was diagnosed as Polymyxin B induced respiratory failure. Polymyxins were stopped, patient was discharged in a stable condition after five days of further observation and is currently on follow up with no such episode of dyspnoea.