The family of serum-glucocorticoid-regulated kinase (SGK) consists of three paralogs, SGK-1, SGK-2, and SGK-3, with SGK-1 being the better studied. Indeed, recognition of the role of SGK-1 in ...regulation of cell survival and proliferation has led to introduction of a number of small-molecule inhibitors for some types of cancer. In addition, SGK-1 regulates major physiologic effects, such as renal solute transport, and contributes to the pathogenesis of non-neoplastic conditions involving major organs including the heart and the kidney. These observations raise the prospect for therapeutic modulation of SGK-1 to reduce the burden of such diseases as myocardial infarction and acute kidney injury. Following a brief description of the structure and function of SGK family of proteins, the present review is primarily focused on our current understanding of the role of SGK-1 in pathologies related to ischemia-reperfusion injury involving several organs (e.g., heart, kidney). The essential role of the mitochondrial permeability transition pore in cell death coupled with the pro-survival function of SGK-1 raise the prospect that its therapeutic modulation could beneficially impact conditions associated with ischemia-reperfusion injury. SIGNIFICANCE STATEMENT: Since the discovery of serum glucocorticoid-regulated kinase (SGK)-1, extensive research has unraveled its role in cancer biology and, thus, its therapeutic targeting. Increasingly, it is also becoming clear that SGK-1 is a major determinant of the outcome of ischemia-reperfusion injury to various organs. Thus, evaluation of existing information should help identify gaps in our current knowledge and also determine whether and how its therapeutic modulation could impact the outcome of ischemia-reperfusion injury.
Summary On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into ...the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
Glucocorticoids are extensively used for a variety of conditions, including those associated with dysregulation of immune and inflammatory responses as primary etiopathogenic factors. Indeed, the ...proinflammatory cytokine storm of coronavirus disease 2019 (COVID-19) is the latest condition for which the use of a glucocorticoid has been advocated. Recognition of serious adverse effects of glucocorticoids has led to research aimed at unraveling molecular basis by which they impact immune and inflammatory events with the ultimate objective of devising novel therapies to circumvent glucocorticoids-related adverse outcomes. Consequently, glucocorticoid-induced leucine zipper (GILZ) protein was discovered and is increasingly recognized as the pivotal regulator of the effects of glucocorticoids on immune and inflammatory responses. Importantly, the advent of GILZ-based options raises the prospect of their eventual therapeutic use for a variety of conditions accompanied with dysregulation of immune and inflammatory responses and associated target organ complications. Thus, the objective of this minireview is to describe our current understanding of the role of GILZ in the cardiovascular system and the kidney along with outcome of GILZ-based interventions on associated disorders. This information is also of relevance for emerging complications of COVID-19. SIGNIFICANCE STATEMENT: Glucocorticoid-induced leucine zipper (GILZ) was initially discovered as the pivotal mediator of immune regulatory/suppressive effects of glucocorticoids. Since the use of glucocorticoids is associated with serious adverse effects, GILZ-based formulations could offer therapeutic advantages. Thus, this minireview will describe our current understanding of the role of GILZ in the kidney and the cardiovascular system, which is of relevance and significance for pathologies affecting them, including the multiorgan complications of coronavirus disease 2019.
Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target ...populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism's reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs).
To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16(INK4a) and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential.
Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs.
In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.
•Ga, Al, and Cr substituted hexaferrites were prepared by ball milling and calcination.•Al ions results in a maximum increase in coercivity and decrease in magnetization.•The anisotropy field is ...almost constant for all substitutions.•The first anisotropy constant is proportional to the saturation magnetization.•The magnetic properties have potential applications in permanent magnet applications.
M-type hexaferrites BaFe12−xMxO19 (M=Ga, Al, Cr) were prepared by ball milling and sintering. X-ray diffraction patterns indicated the formation of the hexaferrite phase at a sintering temperature of 1100°C, with small amounts of α-Fe2O3 secondary phase in the Al and Cr substituted hexaferrites. Scanning electron microscopy indicated that the particle size does not change with Ga substitution, and decreases with increasing Al and Cr substitutions. The atomic ratios determined by energy dispersive X-ray spectroscopy were close to stoichiometric ratios. Mössbauer spectra were used to determine the site preference for each type of cationic substitution. The results of the magnetic measurements indicated constancy of the anisotropy filed and similarity of the behaviors of the first anisotropy constant (K1) and the saturation magnetization with increasing substitution level for all types of substitutions. The coercivity was found to increase with increasing the concentrations of the substituents, and a maximum increase in the coercivity for the Al substituted hexaferrites was observed.
Summary The Rohingya people of Myanmar (known as Burma before 1989) were stripped of citizenship in 1982, because they could not meet the requirement of proving their forefathers settled in Burma ...before 1823, and now account for one in seven of the global population of stateless people. Of the total 1·5 million Rohingya people living in Myanmar and across southeast Asia, only 82 000 have any legal protection obtained through UN-designated refugee status. Since 2012, more than 159 000 people, most of whom are Rohingya, have fled Myanmar in poorly constructed boats for journeys lasting several weeks to neighbouring nations, causing hundreds of deaths. We outline historical events preceding this complex emergency in health and human rights. The Rohingya people face a cycle of poor infant and child health, malnutrition, waterborne illness, and lack of obstetric care. In December, 2014, a UN resolution called for an end to the crisis. We discuss the Myanmar Government's ongoing treatment of Rohingya through the lens of international law, and the steps that the newly elected parliament must pursue for a durable solution.
Abstract
A highly stable and magnetized citric acid (CA)-functionalized iron oxide aqueous colloidal solution (Fe
3
O
4
@CA) was synthesized by using a simple and rapid method of one-step ...co-participation via a chemical reaction between Fe
3+
and Fe
2+
in a NaOH solution at 65 °C, followed by CA addition to functionalize the Fe
3
O
4
surface in 25 min. The NPs were synthesized at lower temperatures and shortened time compared with conventional methods. Surface functionalization is highly suggested because bare Fe
3
O
4
nanoparticles (Fe
3
O
4
NPs) are frequently deficient due to their low stability and hydrophilicity. Hence, 19 nm-sized Fe
3
O
4
NPs coated with CA (Fe
3
O
4
@CA) were synthesized, and their microstructure, morphology, and magnetic properties were characterized using X-ray diffraction, transmission electron microscopy, Zeta potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. CA successfully modified the Fe
3
O
4
surface to obtain a stabilized (homogeneous and well dispersed) aqueous colloidal solution. The Zeta potential value of the as-prepared Fe
3
O
4
@CA increases from − 31 to − 45 mV. These CA-functionalized NPs with high magnetic saturation (54.8 emu/g) show promising biomedical applications.
•The lightly reinforced-SFRC slabs attained the designed moment redistribution.•The lightly reinforced-SFRC slabs showed a softening behaviour after the peak load.•The ductility of the R-SFRC slabs ...decreased with increasing moment redistribution.•The post-peak behaviour of R-SFRC flexural members was formulated mathematically.•The AS 3600:2018 predicted the capacity of R-SFRC slabs with reasonable accuracy.
The ductility and post-peak behaviour of conventionally reinforced steel fibre reinforced concrete (R-SFRC) flexural members have been found to be dependent on the volume of tensile reinforcement. Although few studies have investigated the effect of low reinforcement volume on the ductility and post-peak behaviour of simply supported and continuous members, no study was found for continuous members that were designed for moment redistribution. Further, no prior studies have investigated the ability of lightly reinforced-SFRC continuous members to redistribute moment, or if the achievement of the maximum amount of moment redistribution in design standards is possible. Because of the lack of research in this area, strict limitations are placed in standards for moment redistribution in lightly reinforced-SFRC continuous members. Thus, an experimental study was undertaken for six full-scale two-span continuous one-way slabs with the objectives of determining the moment redistribution capability of lightly reinforced-SFRC continuous members and effect of low reinforcement volume on the ductility and post-peak behaviour of R-SFRC continuous members. The nominal dosage of steel fibres in the R-SFRC slabs was 60 kg/m3 and the tensile reinforcement ratios were between 0.0021 and 0.0042 to provide for bending moment redistribution up to 30% of the linear elastic bending moments. The test results showed that the lightly reinforced-SFRC slabs achieved the designed and maximum amount of moment redistributions and had sufficient ductility, but the R-SFRC slabs showed a softening behaviour after the ultimate load whereas the reinforced concrete (RC) slabs showed a hardening behaviour. Consequently, the post-peak behaviour of R-SFRC flexural members was formulated mathematically. Finally, the rectangular stress block model of AS 3600:2018 was found to determine the capacity of the R-SFRC slabs with reasonable accuracy.
Sonochemistry uses ultrasound to improve or modify chemical reactions. Sonochemistry occurs when the ultrasound causes chemical effects on the reaction system, such as the formation of free radicals, ...that intensify the reaction. Many studies have investigated the synthesis of nanomaterials by the sonochemical method, but there is still very limited information on the detailed characterization of these physicochemical and morphological nanoparticles. In this comprehensive review, recent advances in the sonochemical synthesis of nanomaterials based on iron oxide nanoparticles (Fe
O
NP), gold nanoparticles (AuNP) and iron oxide-coated gold nanoparticles (Fe
O
@Au NP) are discussed. These materials are the most studied materials for various applications, such as medical and commercial uses. This review will: (1) address the simple processing and observations on the principles of sonochemistry as a starting point for understanding the fundamental mechanisms, (2) summarize and review the most relevant publications and (3) describe the typical shape of the products provided in sonochemistry. All in all, this review's main outcome will provide a comprehensive overview of the available literature knowledge that promotes and encourages future sonochemical work.
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