Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Left ventricular mass : correlation with fatness, hemodynamics and renal morphology

Background: Left ventricular mass (LVM) is correlated with body composition and central hemodynamics as well as kidney function. Recently, fat-free mass has been considered to be more strongly correlated with LVM in comparison to other descriptors of fatness. We therefore address the question of whether comprehensive descriptors of fatness, central hemodynamics and renal characteristics demonstrate the association with left ventricular mass in healthy non-obese population. Material/Methods: 119 healthy non-obese subjects (53 females, 66 males, mean age 50 yrs) were evaluated. Central hemodynamics was measured by Pulse Wave Analysis, left ventricular mass was assessed by echocardiography, fatness was evaluated by anthropometry, bioimpedance, and ultrasound. Results: Left ventricular mass index (LVMI) correlated to the same extent with central and peripheral blood pressure but not with descriptors of wave reflection. Fat-free mass as well as intraabdominal fat correlated to a similar extent with LVMI. Kidney morphological characteristics indexed to body surface area were associated inversely and independently with LVMI. Conclusions: Comprehensive assessment of fatness reinforced the concept that intraabdominal fat compartment is strongly correlated with left ventricular mass. Descriptors of wave reflection are not associated with left ventricular mass. The interrelationsh between kidney morphology and LVMI indicates that such associations may be a biologically plausible phenomenon

Body Condition and Breeding of Urban Red Squirrels: Comparison of Two Populations Affected by Different Levels of Urbanization

The red squirrel is among the mammals that have adjusted well to urban habitats. Here, we focused on the two populations inhabiting Warsaw: in a park (with year-round supplemental feeding) and in an urban forest. We hypothesised that park squirrels would have higher body mass (and better body condition), being more stable over the year, and would have a higher breeding rate (i.e., the share of breeding females). Contrary to our hypothesis, forest squirrels were heavier and had better body condition than park squirrels. The body masses of squirrels from both areas were quite stable (with the highest values obtained in spring). Females in better body conditions were more likely to breed. More breeding females and sub-adults were trapped in the park. Regardless of the study site, the highest share of breeding females was in spring, but they also bred in winter and in the remaining seasons. The lower body mass/condition of park squirrels may be possibly explained by high intraspecific competition, or by stable food (and thermal as typical for the city) conditions, in which accumulating fat was not crucial. Mild winter conditions may have also enabled squirrels to breed early. This study showed the high plasticity of red squirrels living in human-transformed habitats

Remote and on-site work stress severity during the COVID-19 pandemic: comparison and selected conditions

Objectives The aim of the present study was to explore whether remote and on-site work stress during the COVID-19 pandemic was experienced with different severity. The second goal was to investigate stress conditions at both working modes. Material and Methods The study involved 946 individuals working in the education system and BSS sector in different Polish organizations. The following tools were used: the Brief Scale of Vocational Stress by Dudek and Hauk, the Polish version of the scales to measure work–family conflicts by Grzywacz, Frone, Brewer and Kovner, Meyer and Allen’s Affective, Continuance, and Normative Commitment Scales in the Polish adaptation by Bańka, Wołowska and Bazińska, the Satisfaction with Job Scale by Zalewska. Results The analysis of intergroup differences revealed that remote work stress severity was significantly lower than on-site work stress severity. The regression analyses proved that work–family conflict and job satisfaction were significant predictors of remote and on-site work stress. Continuance commitment positively predicted on-site work stress. Both models turned out to be statistically significant. The variables included in the models explained 39% and 35% of the variability of the remote work and on-site work stress, respectively. Conclusions Remote work is associated with lower stress severity than on-site work. For both types of work, the higher the level of work–family conflict, the higher the level of stress severity, but the higher the job satisfaction, the lower the stress severity. Continuance commitment is positively related to on-site stress, which means that people who work for an organization and see no alternative feel more stressed. Such an effect was observed only in the case of on-site work. The study findings are discussed in light of previous research, and implications for organizational practice are considered. Int J Occup Med Environ Health. 2023;36(1):96–11

Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose

Urolithins are bioactive compounds generated in human and animal intestines because of the bacterial metabolism of dietary ellagitannins (and their constituent, ellagic acid). Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglycative properties, urolithins are potential novel therapeutic agents. In this study, while considering the future possibility of using urolithins to improve podocyte function in diabetes, we assessed the results of exposing mouse podocytes cultured in normal (NG, 5.5 mM) and high (HG, 25 mM) glucose concentrations to urolithin A (UA) and urolithin B (UB). Podocytes metabolized UA to form glucuronides in a time-dependent manner; however, in HG conditions, the metabolism was lower than in NG conditions. In HG milieu, UA improved podocyte viability more efficiently than UB and reduced the reactive oxygen species level. Both types of urolithins showed cytotoxic activity at high (100 &micro;M) concentration. The UA upregulated total and surface nephrin expression, which was paralleled by enhanced nephrin internalization. Regulation of nephrin turnover was independent of ambient glucose concentration. We conclude that UA affects podocytes in different metabolic and functional aspects. With respect to its pro-survival effects in HG-induced toxicity, UA could be considered as a potent therapeutic candidate against diabetic podocytopathy

A validated LC–MS/MS method for simultaneous determination of key glucocorticoids in animal hair for applications in conservation biology

Abstract A new method for the determination of main glucocorticoids (cortisol, cortisone, and corticosterone) in hair by liquid chromatography-tandem mass spectrometry was developed. Glucocorticoids were extracted from hair shafts using methanol followed by solid-phase extraction. A validation test was performed using hair from three species of wild mammals with different body size (0.2–800 kg), lifestyle (terrestrial, burrowing and arboreal species), social organization (living in herds or solitary), and different predicted type of hair glucocorticoids: European bison (Bison bonasus), European hamster (Cricetus cricetus), and Eurasian red squirrel (Sciurus vulgaris). Regardless of the species evaluated, the method shows good linearity for all analytes accompanied by satisfactory accuracy (91–114%) and precision (RSD < 13%). Depending on the analyte and hair origin, the calculated limits of quantification were between 0.05 and 1.19 ng/mL, which corresponds to 1.28–31.51 pg/mg. Using cortisol and cortisone as examples, we have demonstrated that measuring multiple glucocorticoids simultaneously provides more comprehensive information than solely concentrating on one, thereby contributing to a more balanced and reliable interpretation of the acquired results. However, the utility of cortisol metabolites as markers of stress response in keratinized tissues should be substantiated by additional experimental studies on targeted animals. We posit that this paper could serve as a crucial catalyst to prompt such experiments

Biotechnological strategies for controlled accumulation of flavones in hairy root culture of Scutellaria lateriflora L.

Abstract Accumulation of medicinally important flavones and acteoside was evaluated in Scutellaria lateriflora hairy root cultures subjected to different experimental strategies – feeding with precursors of phenolics biosynthesis (phenylalanine, cinnamic acid, and sodium cinnamate), addition of elicitors (chitosan, jasmonic acid) and Amberlite XAD-4 and XAD-7 resins and permeabilization with dimethyl sulfoxide (DMSO) and methanol. The production profile of S. lateriflora cultures changed under the influence of the applied strategies. Hairy roots of S. lateriflora were found to be a rich source of wogonoside or wogonin, depending on the treatment used. The addition of sodium cinnamate (1.0 mg/L) was the most effective approach to provide high production of flavonoids, especially wogonoside (4.41% dry weight /DW/; 566.78 mg/L). Permeabilization with DMSO (2 µg/ml for 12 h) or methanol (30% for 12 h) resulted in high biosynthesis of wogonin (299.77 mg/L and 274.03 mg/L, respectively). The obtained results provide new insight into the selection of the optimal growth conditions for the production of in vitro biomass with a significant level of flavone accumulation. The data may be valuable for designing large-scale cultivation systems of hairy roots of S. lateriflora with high productivity of bioactive compounds – wogonin or wogonoside