Interferons (IFNs) have been used for decades to treat polycythemia vera (PV). Single-arm clinical trials assessing IFN in PV patients demonstrated high hematological and molecular response rates, ...indicating potential disease-modifying activity of IFN. However, discontinuation rates of IFNs have been rather high due to frequent treatment-related side-effects.
Ropeginterferon alfa-2b (ROPEG) is a monopegylated IFN consisting of a single isoform, which differentiates it from previous IFNs with respect to tolerability and dosing frequency. ROPEG has improved pharmacokinetic and pharmacodynamic properties, which allow extended dosing every 2 weeks and monthly administration during maintenance phase. This review covers ROPEG's pharmacokinetic and pharmacodynamic properties, presents results of randomized clinical trials (RCT) that evaluated ROPEG in the treatment of PV patients, and discusses contemporary findings regarding the potential disease-modifying activity of ROPEG.
RCT have demonstrated high rates of hematological and molecular responses in PV patients treated with ROPEG, irrespective of thrombotic risk. Drug discontinuation rates were generally low. However, even though RCT captured the most important surrogate endpoints of thrombotic risk and disease progression in PV, they were not statistically powered to fully determine whether therapeutic intervention with ROPEG indeed has a direct positive effect on these important clinical outcomes.
Studies have shown that the clinical impact of Janus kinase 2 (JAK2) inhibitors in primary myelofibrosis patients is due to the regulation of cytokine levels, suggesting that cytokine profiles might ...play a critical role in myeloproliferative neoplasms (MPNs) physiopathology. In this study, we compared the plasma cytokine profiles of polycythemia vera (PV) patients and essential thrombocythemia (ET) patients as a function of their JAK2 V617F status and the presence of thrombohemorrhagic complications. Using a multiplex cytokine assay, cytokine measurements were taken of the plasma of 17 PV patients and 21 ET patients. Twenty-two of these patients (10 PV and 12 ET) experienced at least one thrombohemorrhagic manifestation before diagnosis. We showed that cytokine levels were significantly increased in PV and ET patients compared with normal values and that several positive correlations existed between the cytokine concentrations and the biological parameters in each MPN. The comparison between the cytokine profiles of ET and PV patients showed a statistically significant increase of interleukin (IL)-4, IL-8, granulocyte macrophage–colony stimulating factor, interferon -γ, monocyte chemotactic protein -1, platelet derived growth factor-BB, and vascular endothelial growth factor in the ET group. Only tumor necrosis factor-α and platelet derived growth factor-BB were specifically impacted by the JAK2 V617F status of the PV and ET patients, respectively, suggesting that there are both JAK2 V617F–driven and JAK2 V617F–independent inflammatory responses in MPNs. We also showed that the subgroup of PV patients with vascular complications displayed significantly different concentrations of IL-12(p70) and granulocyte macrophage–colony stimulating factor compared with patients without vascular complications. Altogether, these data suggest that cytokine measurement might be useful for the clinical and therapeutic stratification of PV and ET patients.
The application of alginate-based coatings in food preservation is limited owing to their poor antimicrobial, UV-shielding, and water-barrier properties. For this concern, multifunctional alginate ...films were designed for the preservation of green capsicums through the incorporation of aloe vera (AV) and frankincense oil (FO). FTIR confirmed the successful incorporation of AV and FO while XRD showed a crystallinity reduction in the presence of FO. Significant improvements in thermal stability and mechanical properties were achieved in the presence of AV and FO. The addition of AV and FO made the films more bright, yellow and green meanwhile the film's transparency was not significantly influenced. A significant UV-shielding was detected upon increasing either AV or FO. Water vapor permeability was significantly reduced from 21.53 ± 1.43 g mm/m2 day kPa for alginate to 8.18 ± 0.24 g mm/m2 day kPa for the film containing AV at 67% and FO at 6%. Excellent inhibition activities against different bacteria and fungi were obtained for the films containing AV and FO. The prepared films exhibited excellent senescence retardation and resistance to the mass loss for green capsicums. Due to their enhanced UV-barrier, physical and microbial-inhibition properties, the prepared active films might be potentially used in food preservation.
•Aloe vera (AV) and frankincense oil (FO) were incorporated into alginate edible coating.•AV and FO improved UV-shielding, physical and antimicrobial properties.•Both FO and AV didn't significantly affect the film's transparency.•The prepared coating retarded senescence of green capsicums.•The prepared coating might used potentially in food packaging industries.
indent In the present communication, a ternary nanocomposite (NCs) of Strontium oxide (SrO), Barium oxide (BaO), and Aluminium oxide (Al2O3) were synthesized and their photoluminescence and ...electrochemical analysis were performed for display and supercapacitor applications. The NCs were synthesized by solution combustion method using both chemical (SBA-U) and green extract as a fuel/reducing agent (SBA-A). The synthesized sample is subjected to calcination at 600 ° C for 3 h. The Bragg reflections of the synthesized NCs can be attributed to hexagonal SrO, tetragonal BaO and spinel cubic γAl2O3. The SEM image clearly shows the presence of agglomerated irregular size and shaped NPs. The agglomeration was found to be more in SBA-U NCs rather than SBA-A NCs. The direct energy band gap was determined from UV-visible absorption spectra using Wood and Tauc’s relation. The estimated energy band gap was found to be less in SBA-A (3.81 eV) than that of SBA-U NCs (3.88 eV). Further, photoluminescence emission spectra recorded at 300 nm excitation wavelength consist of the high-intensity peak in the green region whereas satellite peaks in blue and red regions. However, the CIE plot and color-correlated temperature confirm the present synthesized NCs are promising candidates for display technology as a green phosphor material. Further, electrochemical studies were performed and the supercapacitance value was determined, which varied within the range of 97.2 to 59.6 F/g at different scan rates. Even though the fuel/reducing agent shows their effect on the intensity of photoluminescence spectra, no such variations are observed in the electrochemical studies. The synthesized samples from both methods might find an application in display and supercapacitor applications.
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•SrO/BaO/Al2O3 nanocomposites are synthesized by aloe vera mediated solution combustion method.•The green emission is observed through photoluminescence analysis, CIE and CCT.•The present material serves as a promising candidate for application in the display technology.•The electrochemical analysis was performed for the supercapacitor application.
Aloe vera is one of numerous feed supplements that can be used to increase productivity and disease resistance in domesticated animals. To reap these advantages, there are various indications, which ...include the proper dosage for better efficacy. As stated earlier, the rising demand for animal source protein in practice is largely met by the strengthening of the livestock sector; this demand goes along with higher demand for animal feeds and animal feed additives. For many years, livestock keepers have been using chemical derivatives and antibiotics to treat their animals against many animal diseases. But the misuse of antibiotics and poor handling of chemical derivatives in different fields has led to tremendous effects, which include adverse effects on animals, plants, the environment, and the final consumer. Herbs are plant sources of safer and inexpensive compounds, so many herbal products have been reported worldwide to enhance several actions such as anti-stress, tonic, antimicrobial, growth stimulant, and immune stimulant in livestock rearing. So many medicinal plant extracts have been tested recently for animal growth performance, immune stimulation, anti-inflammatory, antioxidant, and disease resistance, which have offered good results and have the potential to reduce the use of antibiotics. Aloe vera is one of the herbs that is rapidly utilized as a feed additive in the livestock sector. The physico-chemical composition of Aloe vera and its health characteristics, such as antioxidant properties, healing, immune responses, antimicrobial properties, and many more benefits in domesticated animals, are briefly well discussed in this review article.
Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis.
, a ...miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the
flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with
flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of
flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the
flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies.
In excess of 90% of patients with polycythaemia vera (PV) express a mutated form of Janus kinase 2 (JAK2), JAK2V617F. Such aberrant proteins offer great potential for the treatment of these diseases; ...however, inhibitors to JAK2 have had limited success in the clinic in terms of curing the disease. To understand the effects of this oncogene in haematopoietic cells with the aim of improving treatment strategies, we undertook a systematic evaluation of the effects of JAK2V617F expression using proteomics. The effects of JAK2V617F on over 5000 proteins and 2000 nuclear phosphopeptide sites were relatively quantified using either SILAC or eight-channel iTRAQ mass spectrometry. Pathway analysis of the proteins identified as changing indicated disruption to the p53 and MYC signalling pathways. These changes were confirmed using orthogonal approaches. The insight gained from this proteomic analysis led to the formation of hypothesis-driven analysis on inhibitor-mediated effects on primary cells from patients with a JAK2V617F mutation. Simultaneous inhibition of MYC and upregulation of p53 led to the preferential extinction of JAK2V617F-positive CD34+ cells, illustrating a potential therapeutic benefit from combined targeting of p53 and MYC.
Interferon (IFN-α) is effective therapy for polycythemia vera (PV) patients, but it is frequently interrupted because of adverse events. To permit the long-term use of IFN, we propose combining low ...doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34+ cell apoptosis. Combination treatment with subtherapeutic doses of Peg IFN-α 2a and Nutlin-3 inhibited PV CD34+ cell proliferation by 50% while inhibiting normal CD34+ cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-α 2a inhibited PV colony formation by 55%-90% while inhibiting normal colony formation by 22%-30%. The combination of these agents also decreased the proportion of JAK2V617F-positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with low doses of Peg IFN-α 2a combined with Nutlin-3 increased phospho-p53 and p21 protein levels in PV CD34+ cells and increased the degree of apoptosis. These 2 reagents affect the tumor suppressor p53 through different pathways with Peg IFN-α 2a activating p38 MAP kinase and STAT1, leading to increased p53 transcription, whereas Nutlin-3 prevents the degradation of p53. These data suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN-α 2a can target PV hematopoietic progenitor cells, eliminating the numbers of malignant hematopoietic progenitor cells.
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