Physiological Body Temperature Research Articles

Influence of Method Thawing to Success Artificial Insemination of Cows

Artificial insemination has been widely known among breeders as an effective reproductive technology by inserting sperm collected from male animals into the reproductive tract of female animals for the purpose of improving genetic quality. The success of AI is influenced by several factors, namely semen quality, inseminator expertise, livestock health, and other supporting factors. Good semen quality is one of the determining factors for the success of artificial insemination. One of the quality standards for frozen semen according to SNI is the level of motility post thawing minimum 40%. Motility level post thawing very dependent on technique thawing used. Thawing is the process of re-thawing frozen semen at physiological body temperature to reactivate sperm cells. Thawing can have an impact on reducing the quality of spermatozoa if not done properly. Temperature and time accuracy thawing will maintain sperm viability and motility, so that sperm quality is maintained and the success rate of artificial insemination will be high.

Evolutionary engineering and characterization of Sendai virus mutants capable of persistent infection and autonomous production

Persistent virus infection involves modifying the host immune response and maintaining viral infection. Acute infection with Mononegavirales, such as Sendai viruses (SeVs), can give rise to viruses capable of persistent infection. SeVs establish persistent infection through generating copyback-type defective interfering (cbDI) genomes or acquiring temperature-sensitive mutations. Herein, we identify novel mutations associated with persistent infection and recombinant SeV mutants capable of persistent infection and autonomous production at physiological body temperature, independent of cbDI genomes or temperature-sensitive mutations. Diverse SeV populations were generated by passing the cDNA-recovered SeV Z strain 19 times through embryonated chicken eggs and subsequently infecting LLC-MK2 cells with the SeV populations to finally obtain SeV mutants capable of persistent infection and autonomous production in several types of cultured cells. Sequence analysis identified 4 or 5 mutations in the genome of the persistently infectious SeVs, distinguishing them from other existing strains with persistent infection. Recombinant SeVs carrying 4 or 5 mutations in the Z strain genome (designated SeV-Zpi or SeV-Zpi2, respectively) exhibited persistent infection and autonomous production in LLC-MK2, BHK-21, and Neuro2a cells at 37°C. SeV-Zpi and SeV-Zpi2 consistently produced viral particles even after long-term passages without cbDI particles or temperature-sensitive phenotypes. These results highlight the ability of acute infections of SeVs to spontaneously acquire mutations during replication, thereby endowing persistent infection and autonomous production at body temperature. The vectorization of SeV-Zpi and SeV-Zpi2 will contribute to both basic research and medical applications.

Temperature-Dependent Upregulation of Per2 Protein Expression Is Mediated by eIF2α Kinases PERK and PKR through PI3K Activation.

Temperature-dependent translational control of the core clock gene Per2 plays an important role in establishing entrainment of the circadian clock to physiological body temperature cycles. Previously, we found an involvement of the phosphatidylinositol 3-kinase (PI3K) in causing Per2 protein expression in response to a warm temperature shift (WTS) within a physiological range (from 35 to 38.5 °C). However, signaling pathway mediating the Per2 protein expression in response to WTS is only sparsely understood. Additional factor(s) other than PI3K remains unknown. Here we report the identification of eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), as a novel mediator of WTS-dependent Per2 protein expression. Canonically, eIF2α has been regarded as a major downstream target of PERK and PKR. However, we found that PERK and PKR mediate WTS response of Per2 in a manner not involving eIF2α. We observed that PERK and PKR serve as an upstream regulator of PI3K rather than eIF2α in the context of WTS-dependent Per2 protein expression. There have been studies reporting PI3K activation occurring depending on PERK and PKR, while its physiological contribution has remained elusive. Our finding therefore not only helps to enrich the knowledge of how WTS affects Per2 protein expression but also extends the region of cellular biology involving the PERK/PKR-mediated PI3K activation to include entrainment-mechanism of the circadian clock.

A Complete Sojorum on Thermosensitive Hydrogels for Wound Healing: Recent Developments and Ongoing Research

Abstract: The nature of the wound typically dictates the available wound-healing therapies. On the other hand, inadequate care results in persistent wounds, fibrosis, tissue loss of function, and ultimately dismemberment. Suturing, unloading, irrigation, debridement, negative pressure therapies, growth factor supplementation, and grafting are examples of current medicines that all have limitations in terms of meeting the needs of full treatment. Natural or synthetic materials/polymers have been utilized to prepare smart thermosensitive hydrogels to facilitate quick and targeted action on wounds. These are intelligent hydrogel system that shows sol-gel transitions at physiological body temperature. Hydrogel provides a moist environment, scaffold-like structure, and localized delivery of drug/growth factor that speed up wound healing even if it eliminates side effects associated with systemic administration. In this article, we summarized the detailed mechanisms of wound healing, conventional strategies, and ongoing thorough research work in the field of thermosensitive hydrogels utilized for wound healing. Moreover, the clinical needs of this formulation, as evident from the commercially available systems are also described in the prior art.

Thermoresponsive Alginate-Graft-pNIPAM/Methyl Cellulose 3D-Printed Scaffolds Promote Osteogenesis In Vitro.

In this work, a sodium alginate-based copolymer grafted by thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains was used as gelator (Alg-g-PNIPAM) in combination with methylcellulose (MC). It was found that the mechanical properties of the resulting gel could be enhanced by the addition of MC and calcium ions (Ca2+). The proposed network is formed via a dual crosslinking mechanism including ionic interactions among Ca2+ and carboxyl groups and secondary hydrophobic associations of PNIPAM chains. MC was found to further reinforce the dynamic moduli of the resulting gels (i.e., a storage modulus of ca. 1500 Pa at physiological body and post-printing temperature), rendering them suitable for 3D printing in biomedical applications. The polymer networks were stable and retained their printed fidelity with minimum erosion as low as 6% for up to seven days. Furthermore, adhered pre-osteoblastic cells on Alg-g-PNIPAM/MC printed scaffolds presented 80% viability compared to tissue culture polystyrene control, and more importantly, they promoted the osteogenic potential, as indicated by the increased alkaline phosphatase activity, calcium, and collagen production relative to the Alg-g-PNIPAM control scaffolds. Specifically, ALP activity and collagen secreted by cells were significantly enhanced in Alg-g-PNIPAM/MC scaffolds compared to the Alg-g-PNIPAM counterparts, demonstrating their potential in bone tissue engineering.

Predicting CPAP failure after less invasive surfactant administration (LISA) in preterm infants by machine learning model on vital parameter data: a pilot study

Objective. Less invasive surfactant administration (LISA) has been introduced to preterm infants with respiratory distress syndrome on continuous positive airway pressure (CPAP) support in order to avoid intubation and mechanical ventilation. However, after this LISA procedure, a significant part of infants fails CPAP treatment (CPAP-F) and requires intubation in the first 72 h of life, which is associated with worse complication free survival chances. The aim of this study was to predict CPAP-F after LISA, based on machine learning (ML) analysis of high resolution vital parameter monitoring data surrounding the LISA procedure. Approach. Patients with a gestational age (GA) <32 weeks receiving LISA were included. Vital parameter data was obtained from a data warehouse. Physiological features (HR, RR, peripheral oxygen saturation (SpO2) and body temperature) were calculated in eight 0.5 h windows throughout a period 1.5 h before to 2.5 h after LISA. First, physiological data was analyzed to investigate differences between the CPAP-F and CPAP-Success (CPAP-S) groups. Next, the performance of two types of ML models (logistic regression: LR, support vector machine: SVM) for the prediction of CPAP-F were evaluated. Main results. Of 51 included patients, 18 (35%) had CPAP-F. Univariate analysis showed lower SpO2, temperature and heart rate variability (HRV) before and after the LISA procedure. The best performing ML model showed an area under the curve of 0.90 and 0.93 for LR and SVM respectively in the 0.5 h window directly after LISA, with GA, HRV, respiration rate and SpO2 as most important features. Excluding GA decreased performance in both models. Significance. In this pilot study we were able to predict CPAP-F with a ML model of patient monitor signals, with best performance in the first 0.5 h after LISA. Using ML to predict CPAP-F based on vital signals gains insight in (possibly modifiable) factors that are associated with LISA failure and can help to guide personalized clinical decisions in early respiratory management.

Evidence-based severity assessment of the forced swim test in the rat.

The forced swim test (FST) is a traditional assay, which has been used for more than 40 years to assess antidepressant effects of novel drug candidates. In recent years, a debate about the test has focused on the assumption that the FST is highly aversive and burdening for the animals because of the earlier anthropomorphic interpretation and designation as a "behavioral despair test". The Directive 2010/63/EU and the German Animal Welfare law require a prospective severity classification of the planned experimental procedures. Still, an objective examination of the animals' burden in this test has not been performed yet. To fill this gap, we conducted an evidence-based severity assessment of the forced swim test in rats according to a 'standard protocol' with a water temperature of 25°C. We examined parameters representing the physiological and the affective state, and natural as well as locomotion-associated behaviors in three separate experiments to reflect as many dimensions as possible of the animal's condition in the test. Hypothermia was the only effect observed in all animals exposed to the FST when using this standard protocol. Additional adverse effects on body weight, food consumption, and fecal corticosterone metabolite concentrations occurred in response to administration of the antidepressant imipramine, which is frequently used as positive control when testing for antidepressant effects of new substances. We conclude that this version of the FST itself is less severe for the animals than assumed, and we suggest a severity classification of 'moderate' because of the acute and short-lasting effects of hypothermia. To refine the FST according to the 3Rs, we encourage confirming the predictive validity in warmer water temperatures to allow the rats to maintain physiological body temperature.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Granulosa cell-derived extracellular vesicles mitigate the detrimental impact of thermal stress on bovine oocytes and embryos.

Climate change-induced global warming results in rises in body temperatures above normal physiological levels (hyperthermia) with negative impacts on reproductive function in dairy and beef animals. Extracellular vesicles (EVs), commonly described as nano-sized, lipid-enclosed complexes, harnessed with a plethora of bioactive cargoes (RNAs, proteins, and lipids), are crucial to regulating processes like folliculogenesis and the initiation of different signaling pathways. The beneficial role of follicular fluid-derived EVs in inducing thermotolerance to oocytes during in vitro maturation (IVM) has been evidenced. Here we aimed to determine the capacity of in vitro cultured granulosa cell-derived EVs (GC-EVs) to modulate bovine oocytes' thermotolerance to heat stress (HS) during IVM. Moreover, this study tested the hypothesis that EVs released from thermally stressed GCs (S-EVs) shuttle protective messages to provide protection against subsequent HS in bovine oocytes. For this, sub-populations of GC-EVs were generated from GCs subjected to 38.5°C (N-EVs) or 42°C (S-EVs) and supplemented to cumulus-oocyte complexes (COCs) matured in vitro at the normal physiological body temperature of the cow (38.5°C) or HS (41°C) conditions. Results indicate that S-EVs improve the survival of oocytes by reducing ROS accumulation, improving mitochondrial function, and suppressing the expression of stress-associated genes thereby reducing the severity of HS on oocytes. Moreover, our findings indicate a carryover impact from the addition of GC-EVs during oocyte maturation in the development to the blastocyst stage with enhanced viability.

Minimal upstream open reading frame of Per2 mediates phase fitness of the circadian clock to day/night physiological body temperature rhythm

Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C-38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5' UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology.

Internet of things based real-time coronavirus 2019 disease patient health monitoring system

&lt;span lang="EN-US"&gt;The coronavirus disease (COVID-19) outbreak has led to many infected worldwide and has become a global crisis. COVID-19 manifests in the form of shortness of breath, coughing and fever. More people are getting infected and healthcare systems worldwide are overwhelmed as healthcare workers become exhausted and infected. Thus, remote monitoring for COVID-19 patients is required. An internet of things (IoT) based real-time health monitoring system for COVID-19 patients was proposed. It features monitoring of five physiological parameters, namely electrocardiogram (ECG), heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and body temperature. These vitals are processed by the main controller and transmitted to the cloud for storage. Healthcare professionals can read real-time patient vitals on the web-based dashboard which is equipped with an alert service. The proposed system was able to transmit and display all parameters in real-time accurately without any packet loss or transmission errors. The accuracy of body temperature readings, RR, SpO2 and HR, is up to 99.7%, 100%, 97.97% and 98.34%, respectively. Alerts were successfully sent when the parameters reached unsafe levels. With the proposed system, healthcare professionals can remotely monitor COVID-19 patients with greater ease, lessen their exposure to the pathogen, and improve patient monitoring.&lt;/span&gt;

Antibacterial activity of silver nitrate on Pseudomonas aeruginosa bacteria using Calvet calorimetry

This study aimed to use microcalorimetry to analyze the real-time effect that silver nitrate has on one of the most common bacteria involved in severe infections in current medical practice. Using a Calvet microcalorimeter, the heat output produced by Pseudomonas aeruginosa was determined when exposed to concentrations of silver nitrate from 0 to 3 mol⋅m−3, and a saturated solution. Under physiological human body temperature, for 46 h, thermographic curves were obtained. The maximum voltage peaks (Vmax) and the total amount of heat exchanged (Q) were determined. The results showed a bactericidal effect, with a minimum inhibitory concentration (MIC) of silver nitrate of 0.75 mol⋅m−3, showing a Vmax of 93 μV and Q of 193 kJ. With higher concentrations of this metallic solution, the results highlighted the proportional negative effect that silver nitrate has in Pseudomonas aeruginosa growth.

Estimating core body temperature using electrocardiogram signals.

Suppressing the elevation in core body temperature is an important factor in preventing heatstroke. However, there is still no non-invasive method to sense core body temperature. This study proposed an algorithm that estimates core body temperature based on electrocardiogram signals. A total of 12 healthy men (mean age ± SD = 39.6 ± 13.4) performed an ergometric exercise load test under two conditions of exercise load in an environmental chamber adjusted to a temperature of 35°C and humidity of 50%. Vital sensing data such as electrocardiograms, core body temperatures, and body surface temperatures were continuously measured, and physical data such as body weight were obtained from participants pre- and post-experiment. According to basic physiological knowledge, heart rate and body temperature are closely related. We analyzed the relationship between core body temperature and several indexes obtained from electrocardiograms and found that the amount of change in core body temperature had a strong relationship with analyzed data from electrocardiograms. Based on these findings, we developed the amount of change in core body temperature estimation model using multiple regression analysis including the Poincaré plot index of the ECG R-R interval. The estimation model showed an average estimation error of -0.007°C (average error rate = -0.02%) and an error range of 0.457–0.445°C. It is suggested that continuous core body temperature change can be estimated using electrocardiogram signals regardless of individual characteristics such as age and physique. Based on this applicable estimation model, we plan to enhance estimation accuracy and further verify efficacy by considering clothing and environmental conditions.

Reduced Bone Mass in Collagen Prolyl 4-Hydroxylase P4ha1 +/-; P4ha2 -/- Compound Mutant Mice.

ABSTRACTProper deposition of the extracellular matrix and its major components, the collagens, is essential for endochondral ossification and bone mass accrual. Collagen prolyl 4‐hydroxylases (C‐P4Hs) hydroxylate proline residues in the ‐X‐Pro‐Gly‐ repeats of all known collagen types. Their product, 4‐hydroxyproline, is essential for correct folding and thermal stability of the triple‐helical collagen molecules in physiological body temperatures. We have previously shown that inactivation of the mouse P4ha1 gene, which codes for the catalytic α subunit of the major C‐P4H isoform, is embryonic lethal, whereas inactivation of the P4ha2 gene produced only a minor phenotype. Instead, mice with a haploinsufficiency of the P4ha1 gene combined with a homozygous deletion of the P4ha2 gene present with a moderate chondrodysplasia due to transient cell death of the growth plate chondrocytes. Here, to further characterize the bone phenotype of the P4ha1 +/−; P4ha2 −/− mice, we have carried out gene expression analyses at whole‐tissue and single‐cell levels, biochemical analyses, microcomputed tomography, histomorphometric analyses, and second harmonic generation microscopy to show that C‐P4H α subunit expression peaks early and that the C‐P4H deficiency leads to reduced collagen amount, a reduced rate of bone formation, and a loss of trabecular and cortical bone volume in the long bones. The total osteoblast number in the proximal P4ha1 +/−; P4ha2 −/− tibia and the C‐P4H activity in primary P4ha1 +/−; P4ha2 −/− osteoblasts were reduced, whereas the population of osteoprogenitor colony‐forming unit fibroblasts was increased in the P4ha1 +/−; P4ha2 −/− marrow. Thus, the P4ha1 +/−; P4ha2 −/− mouse model recapitulates key aspects of a recently recognized congenital connective tissue disorder with short stature and bone dysplasia caused by biallelic variants of the human P4HA1 gene. Altogether, the data demonstrate the allele dose‐dependent importance of the C‐P4Hs to the developing organism and a threshold effect of C‐P4H activity in the proper production of bone matrix. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Evaluation of Auditory Brainstem Response in Chicken Hatchlings.

The auditory brainstem response (ABR) is an invaluable assay in clinical audiology, non-human animals, and human research. Despite the widespread use of ABRs in measuring auditory neural synchrony and estimating hearing sensitivity in other vertebrate model systems, methods for recording ABRs in the chicken have not been reported in nearly four decades. Chickens provide a robust animal research model because their auditory system is near functional maturation during late embryonic and early hatchling stages. We have demonstrated methods used to elicit one or two-channel ABR recordings using subdermal needle electrode arrays in chicken hatchlings. Regardless of electrode recording configuration (i.e., montage), ABR recordings included 3-4 positive-going peak waveforms within the first 6 ms of a suprathreshold click stimulus. Peak-to-trough waveform amplitudes ranged from 2-11 µV at high-intensity levels, with positive peaks exhibiting expected latency-intensity functions (i.e., increase in latency as a function of decreased intensity). Standardized earphone position was critical for optimal recordings as loose skin can occlude the ear canal, and animal movement can dislodge the stimulus transducer. Peak amplitudes were smaller, and latencies were longer as animal body temperature lowered, supporting the need for maintaining physiological body temperature. For young hatchlings (<3 h post-hatch day 1), thresholds were elevated by ~5 dB, peak latencies increased ~1-2 ms, and peak to trough amplitudes were decreased ~1 µV compared to older hatchlings. This suggests a potential conductive-related issue (i.e., fluid in the middle ear cavity) and should be considered for young hatchlings. Overall, the ABR methods outlined here permit accurate and reproducible recording of in-vivo auditory function in chicken hatchlings that could be applied to different stages of development. Such findings are easily compared to human and mammalian models of hearing loss, aging, or other auditory-related manipulations.

Evaluation of Auditory Brainstem Response in Chicken Hatchlings

The auditory brainstem response (ABR) is an invaluable assay in clinical audiology, non-human animals, and human research. Despite the widespread use of ABRs in measuring auditory neural synchrony and estimating hearing sensitivity in other vertebrate model systems, methods for recording ABRs in the chicken have not been reported in nearly four decades. Chickens provide a robust animal research model because their auditory system is near functional maturation during late embryonic and early hatchling stages. We have demonstrated methods used to elicit one or two-channel ABR recordings using subdermal needle electrode arrays in chicken hatchlings. Regardless of electrode recording configuration (i.e., montage), ABR recordings included 3-4 positive-going peak waveforms within the first 6 ms of a suprathreshold click stimulus. Peak-to-trough waveform amplitudes ranged from 2-11 µV at high-intensity levels, with positive peaks exhibiting expected latency-intensity functions (i.e., increase in latency as a function of decreased intensity). Standardized earphone position was critical for optimal recordings as loose skin can occlude the ear canal, and animal movement can dislodge the stimulus transducer. Peak amplitudes were smaller, and latencies were longer as animal body temperature lowered, supporting the need for maintaining physiological body temperature. For young hatchlings (<3 h post-hatch day 1), thresholds were elevated by ~5 dB, peak latencies increased ~1-2 ms, and peak to trough amplitudes were decreased ~1 µV compared to older hatchlings. This suggests a potential conductive-related issue (i.e., fluid in the middle ear cavity) and should be considered for young hatchlings. Overall, the ABR methods outlined here permit accurate and reproducible recording of in-vivo auditory function in chicken hatchlings that could be applied to different stages of development. Such findings are easily compared to human and mammalian models of hearing loss, aging, or other auditory-related manipulations.

Pharmacodynamics of Xylazine, Acepromazine and Diazepam on Various Physiological Parameter in Rabbits

The aim of the present study was to explore the effect of three selective sedative/tranquilizer drugs i.e. Xylazine(XZ), Acepromazine(AC), and Diazepam(DZ) on normal physiological parameters such aspulse, respiration, body temperature and serum glucose.All the three drugs i.e. Xylazine, Acepromazine, and Diazepam were used at the dose rate of 8mg/kg, 5 mg/kgand diazepam1mg/kg respectivelythrough intramuscular route(I.M.)in six healthy rabbits of non-descriptive Before administration of drugs all physiological parameters were recordedPulse, respiration and body temperature shows significant (0.05) decrease after administration of these drugs. Maximum decrease in the pulse rate was recorded at 60, 30 and 45 minutes and were returned to its normal at 150, 135 and 135 minutes with XZ, AC and DZ Low respiratory rate was noted at 45, 30 and 75 minutes and were returned to the non-significant level at 105, 90 and 135 minutes with XZ, AC and DZ Body temperature decreased to its maximum at 45, 30 and 60 minutes and returned to its normal at 120, 120 and 135 minutes after administration of XZ, AC and DZ Onset of sedation started at 83±0.30, 6.16±0.47 and 3.83±0.30 minutes with XZ, AC and DZ Significant difference were found in XZ and AC, DZ and AC at 0.05 but there was no significant difference between XZ and Total duration of sedation was 101.17±1.07, 00±1.87 and 90.00±1.29 with XZ, AC and DZ respectively.XZ and DZ significantly (P&lt; 0.05) increase serum glucose level while AC have no significant effect on serum glucose From the overall finding all the three drugs were were found safe for rabbits but XZ shows the best results.

Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators.

Deferoxamine (DFO) is an FDA‐approved iron‐chelating agent which shows good therapeutic efficacy, however, its short blood half‐life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained‐release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol–gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half‐life 47‐fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator‐loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.

Interactions between a biomedical thermoresponsive polymer and imidazolium-based ionic liquids: A comprehensive biophysical investigation

Understanding the phase transition behavior of thermoresponsive polymers (TRPs) and ionic liquids (ILs) aids in the development of novel polymeric ionic liquid (PIL)-based materials. Further, knowledge of the molecular interactions between TRPs and ILs leads to novel biophysical prospects, such as producing TRPs with phase transition behaviors nearer to physiological body temperature that can be employed in drug delivery systems. Predicted interactions between TRPs and ILs were used to probe the changes in the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) upon adding 1-ethyl-3-methylimidazolium nitrate ([Emim][NO3]) or 1-butyl-3-methylimidazolium nitrate ([Bmim][NO3]) ILs to aqueous PNIPAM solutions. Absorption and steady-state fluorescence spectroscopy were used to elucidate molecular interactions and variations in the absorbances of aqueous TRP and IL mixtures, and temperature-dependent dynamic light scattering, and fluorescence spectroscopy measurements were used to determine LCSTs. Aggregation behavior, changes in coil to globule transition behavior, absorbances, and fluorescence intensities were identified in aqueous PNIPAM, PNIPAM-[Emim][NO3] and PNIPAM-[Bmim][NO3] solutions. IL additions increased the LCST of PNIPAM, and this effect was more pronounced in ILs, perhaps due to the shorter alkyl chain on the imidazolium cation. The current study aids the design of PIL-based materials and could stimulate novel developmental concepts.

Smart Magnetic Nanocarriers for Multi-Stimuli On-Demand Drug Delivery

In this study, we report the realization of drug-loaded smart magnetic nanocarriers constituted by superparamagnetic iron oxide nanoparticles encapsulated in a dual pH- and temperature-responsive poly (N-vinylcaprolactam-co-acrylic acid) copolymer to achieve highly controlled drug release and localized magnetic hyperthermia. The magnetic core was constituted by flower-like magnetite nanoparticles with a size of 16.4 nm prepared by the polyol approach, with good saturation magnetization and a high specific absorption rate. The core was encapsulated in poly (N-vinylcaprolactam-co-acrylic acid) obtaining magnetic nanocarriers that revealed reversible hydration/dehydration transition at the acidic condition and/or at temperatures above physiological body temperature, which can be triggered by magnetic hyperthermia. The efficacy of the system was proved by loading doxorubicin with very high encapsulation efficiency (>96.0%) at neutral pH. The double pH- and temperature-responsive nature of the magnetic nanocarriers facilitated a burst, almost complete release of the drug at acidic pH under hyperthermia conditions, while a negligible amount of doxorubicin was released at physiological body temperature at neutral pH, confirming that in addition to pH variation, drug release can be improved by hyperthermia treatment. These results suggest this multi-stimuli-sensitive nanoplatform is a promising candidate for remote-controlled drug release in combination with magnetic hyperthermia for cancer treatment.