Controlling the magnetic properties of a nanoparticle efficiently via its particle size to achieve optimized heat under alternating magnetic field is the central point for magnetic ...hyperthermia-mediated cancer therapy (MHCT). Here, we have shown the successful use of stevioside (a natural plant-based glycoside) as a promising biosurfactant to control the magnetic properties of Fe
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nanoparticles by controlling the particle size. The biocompatibility and cellular uptake efficiency by rat C6 glioma cells and calorimetric magnetic hyperthermia profile of the nanoparticles were further examined. Our finding suggests superior properties of stevioside-coated magnetite nanoparticles in comparison to polysorbate-80 and oleic acid coated nanomagnets as far as particle size reduction, biocompatibility, hyperthermic effect, and cellular uptake by the glioblastoma cancer cells are concerned. The stevioside-coated nanomagnets exhibiting the maximum temperature rise were further investigated as heating agents in in vitro magnetic hyperthermia experiments (405 kHz, 168 Oe), showing their efficacy to induce cell death of rat C6 glioma cells after 30 min at a target temperature T = 43 °C.
Since recurrence and metastasis of pancreatic cancer has a worse prognosis, chemotherapy has been typically performed to attack the remained malignant cells after resection. However, it is difficult ...to achieve the therapeutic concentration at the tumor site with systemic chemotherapy. Numerous local drug delivery systems have been studied to overcome the shortcomings of systemic delivery. However, because most systems involve dissolution of the drug within the carrier, the concentration of the drug is limited to the saturation solubility, and consequently cannot reach the sufficient drug dose. Therefore, we hypothesized that 3D printing of a biodegradable patch incorporated with a high drug concentration would provide a versatile shape to be administered at the exact tumor site as well as an appropriate therapeutic drug concentration with a controlled release. Here, we introduce the 3D-printed patches composed of a blend of poly(lactide-co-glycolide), polycaprolactone, and 5-fluorouracil for delivering the anti-cancer drug in a prolonged controlled manner and therapeutic dose. 3D printing technology can manipulate the geometry of the patch and the drug release kinetics. The patches were flexible, and released the drug over four weeks, and thereby suppressed growth of the subcutaneous pancreatic cancer xenografts in mice with minimized side effects. Our approach reveals that 3D printing of bioabsorbable implants containing anti-cancer drugs could be a powerful method for an effective local delivery of chemotherapeutic agents to treatment of cancers.
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The Weibel instability due to temperature anisotropy of electrons and ions in a plasma in the presence of cold and warm ions is reported. Numerical calculations of the normalized growth rate are ...carried out when the frequency of electromagnetic waves is greater than or less than the thermal velocity of electrons for typical existing plasma parameters. The normalized growth rate increases with an increasing normalized wave number, and after attaining maxima, it decreases due to thermal effects. Therefore, a parabolic plot is obtained for the growth rate. The threshold values of the growth rate depend on the anisotropy parameters. On increasing the value of the temperature anisotropy ratio of either plasma component, the observed growth rate increases. There is a considerable and contrasting effect of the presence of cold and warm ions on the growth rate of the Weibel instability in the plasma. The addition of cold ions stabilizes the instability and reduces the maximum growth rate values, while the addition of warm ions to the plasma increases the instability with a considerable decrease in the domain of instability. Our theoretical investigations of the effect of temperature anisotropy on the growth rate of the Weibel instability are in good agreement with the existing experimental results.
The effect of fluctuations of dust grains on the parametric up conversion of lower hybrid waves into a whistler wave in a complex plasma is studied. In a complex plasma, which contains ambient ...magnetic field, the lower hybrid pump possessing a large amplitude decays into two modes: a whistler wave mode and a lower hybrid wave mode having low frequency. Furthermore, a ponderomotive force is exerted by the lower hybrid pump and whistler side bands on the existing electrons, which drives the lower hybrid decay mode. Furthermore, the coupling of v⃗1, the oscillatory velocity of low-frequency lower hybrid waves, along with the density perturbations, produces a nonlinear current, which drives the whistler mode. The growth rate Γ (sec−1) of lower hybrid waves scales linearly with the amplitude of the pump waves, and it increases as the amplitude of the lower hybrid pump waves increase. Moreover, the dust grain charges influence the instability appreciably. Our theoretically observed growth rate decreases with the increase in the relative density d=n0i/n0e of negatively charged dust grains, while it decreases with the size of dust grains a (μm). The growth rate varies inversely to the electron cyclotron frequency ωce, and it decreases as ωce increases. The results presented in the article are efficiently able to elaborate the basics of the whistler wave excitation in complex plasmas, space plasmas, processing in solid state plasmas, fusion plasmas, and laboratory plasmas as well as industrial plasmas.
In this article, the effect of dust charge fluctuations on the parametric upconversion of a lower hybrid wave into an ion cyclotron wave and a side band wave in a two-ion species tokamak plasma is ...studied. When the oscillatory velocity of plasma electrons is a few percent of the sound velocity, the lower hybrid wave becomes unstable and decays into two modes: an ion cyclotron wave mode and a low frequency lower hybrid side band wave. Furthermore, a ponderomotive force by a lower hybrid pump and a side band wave is exerted on the existing electrons, which drives the ion cyclotron decay mode. The presence of negatively charged dust grains and their shape, size, radius, and density influence the instability. The growth rate of instability is calculated by considering typical existing D–T (Deuterium–Tritium) dusty plasma parameters, and it is observed that the growth rate increases with the relative density of dust grains, number density of dust grains, oscillatory velocity of electrons, and amplitude of pump waves. However, the normalized growth rate increases with the unstable wave frequency, and it also increases as we increase the ratio of deuterium to tritium density. Here, the growth rate decreases with the increase in the size of dust grains and electron cyclotron frequency. The theoretical results summarized in the present study are able to efficiently elaborate the complexity produced in plasma properties in a tokamak due to the dust–plasma interactions, which are briefly discussed here.
When ROS production exceeds the cellular antioxidant capacity, the cell needs to eliminate the defective mitochondria responsible for excessive ROS production. It has been proposed that the removal ...of these defective mitochondria involves mitophagy, but the mechanism of this regulation remains unclear. Here, we demonstrate that moderate mitochondrial superoxide and hydrogen peroxide production oxidates KEAP1, thus breaking the interaction between this protein and PGAM5, leading to the inhibition of its proteasomal degradation. Accumulated PGAM5 interferes with the processing of the PINK1 in the mitochondria leading to the accumulation of PINK1 on the outer mitochondrial membrane. In turn, PINK1 promotes Parkin recruitment to mitochondria and sensitizes mitochondria for autophagic removal. We also demonstrate that inhibitors of the KEAP1-PGAM5 protein-protein interaction (including CPUY192018) mimic the effect of mitochondrial ROS and sensitize mitophagy machinery, suggesting that these inhibitors could be used as pharmacological regulators of mitophagy. Together, our results show that KEAP1/PGAM5 complex senses mitochondrially generated superoxide/hydrogen peroxide to induce mitophagy.
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•Increased mitochondrial ROS production disrupts the KEAP1-PGAM5 complex blocking PGAM5 processing.•Accumulating PGAM5 interferes with PINK1 processing leading to the stabilization of PINK1 on the mitochondrial membrane.•This stimulates Parkin translocation to mitochondria facilitating mitophagy and removal of ROS-producing mitochondria.•KEAP1-PGAM5 protein-protein interaction inhibitors mimic the effect of ROS and sensitize mitochondria to autophagy.
In this paper, we investigate the impact of an external magnetic field on the Weibel instability driven by temperature anisotropy in a magnetized plasma. The study provides the influence of electron ...temperature anisotropy, considering both cold as well as warm ions. We derive expressions for the growth rate Γ (s−1) in each case to quantify the effect of some specific parameters on the instability. For example, the growth rate is plotted against the magnetic field for three distinct cases: considering only electrons, including cold ions, and incorporating warm ions. It is observed that the growth rate decreases as the applied magnetic field increases. Furthermore, the addition of both cold and warm ions to the plasma significantly influences the observed effects. It can be explained as follows: in the presence of cold ions, the growth rate is decreased with an increase in the wave number kz (cm−1). In addition, a decrease in the growth rate is observed with an increasing wave number in the case of warm ions. Therefore, it can be seen that the Weibel instability, propelled by thermal anisotropy, holds significant implications owing to its prevalence in both astrophysical and laboratory plasmas. The findings presented here are expected to contribute to the advancements in magnetic field generation and particle acceleration in various astrophysical phenomena, including gamma-ray bursts, relativistic collisionless shock fronts, radio supernovae, and pulsar winds.
Abstract Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect in Wolfram syndrome involves poor ER Ca 2+ handling, but how this disturbance leads ...to the disease is not known. The current study, performed in primary neurons, the most affected and disease-relevant cells, involving both Wolfram syndrome genes, explains how the disturbed ER Ca 2+ handling compromises mitochondrial function and affects neuronal health. Loss of ER Ca 2+ content and impaired ER-mitochondrial contact sites in the WFS1- or CISD2-deficient neurons is associated with lower IP 3 R-mediated Ca 2+ transfer from ER to mitochondria and decreased mitochondrial Ca 2+ uptake. In turn, reduced mitochondrial Ca 2+ content inhibits mitochondrial ATP production leading to an increased NADH/NAD + ratio. The resulting bioenergetic deficit and reductive stress compromise the health of the neurons. Our work also identifies pharmacological targets and compounds that restore Ca 2+ homeostasis, enhance mitochondrial function and improve neuronal health.
Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of ...Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics.
This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR).
Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/μl vs. 0.2 ng/μl).
This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.
Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C ...particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines.
A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets.
Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively.
Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.
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