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Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury repair process. In the present study, we further observed a marked induction of Rcn3 in the alveolar epithelium during LPS-induced ALI. In vitro alveolar epithelial (MLE-12) cells consistently exhibited a significant induction of Rcn3 accompanied with NF-κB activation in response to LPS exposure. We examined the role of Rcn3 in the alveolar inflammatory response by using mice with a selective deletion of Rcn3 in alveolar epithelial cells upon doxycycline administration. The Rcn3 deficiency significantly blunted the ALI and alveolar inflammation induced by intratracheal LPS instillation but not that induced by an intraperitoneal LPS injection (secondary insult); the alleviated ALI was accompanied by decreases in NF-κB activation and NLRP3 levels but not in GRP78 and cleaved caspase-3 levels. The studies conducted in MLE-12 cells consistently showed that Rcn3 knockdown blunted the activations of NF-κB signaling and NLRP3-dependent inflammasome upon LPS exposure. Collectively, these findings suggest a novel role for Rcn3 in regulating the alveolar inflammatory response to pulmonary infection via the NF-κB/NLRP3/inflammasome axis and shed additional light on the mechanism of ARDS/ALI.Dendritic cell (DC) vaccines are a safe and effective means of inducing tumor immune responses, however, a better understanding of DC biology is required in order to realize their full potential. Recent advances in DC biology have identified a crucial role for cDC1 in tumor immune responses, making this DC subset an attractive vaccine target. Human cDC1 exclusively express the C-type-lectin-like receptor, CLEC9A (DNGR-1) that plays an important role in cross-presentation, the process by which effective CD8+ T cell responses are generated. CLEC9A antibodies deliver antigen specifically to cDC1 for the induction of humoral, CD4+ and CD8+ T cell responses and are therefore promising candidates to develop as vaccines for infectious diseases and cancer. The development of human CLEC9A antibodies now facilitates their application as vaccines for cancer immunotherapy. Here we discuss the recent advances in CLEC9A targeting antibodies as vaccines for cancer and their translation to the clinic.Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We explored the role of autophagy and the efficacy of metformin in cisplatin-induced ototoxicity in cells, zebrafish, and mice. Furthermore, the underlying molecular mechanism of how metformin affects cisplatin-induced ototoxicity was examined. In in vitro experiments, autophagy levels in HEI-OC1 cells were assessed using fluorescence and Western blot analyses. In in vivo experiments, whether metformin had a protective effect against cisplatin ototoxicity was validated in zebrafish and C57BL/6 mice. The results showed that cisplatin induced autophagy activation in HEI-OC1 cells. Metformin exerted antagonistic effects against cisplatin ototoxicity in HEI-OC1 cells, zebrafish, and mice. Notably, metformin activatWith the growing number of older people living with HIV, "What is the most effective geriatric care and the research trend of existing literature?" is a compelling question after 30 years since the first paper related to aging and HIV/AIDS published. Our study aims to apply quantitative and qualitative analysis to explore the knowledge gaps and describes the research interest of gerontology research in the field of HIV. A bibliometric analysis was conducted based on the databased of the Web of Science from 1991 to 2019. The major domains of research areas were visualized by using VOSviewer software. Latent Dirichlet Allocation (LDA) was applied to classify the dataset into topics. There was a rising number of publications about this topic over time. H3B-6527 solubility dmso Our findings indicated that antiretroviral treatment and evaluating quality of life and harm reduction were the major domains regarding care for OPLWH. In addition, the finding highlights the role of social competence in treatment outcomes. Further research needs to tailor multi-disciplinary programs and flexible interventions to reduce the burden and the mortality rate of HIV/AIDS.
To develop elite mutant in
having morphotype and oil content of
, and oil quality of
.
The dormant runner of menthol rich genotype MPK-5 were subjected to different doses of γ- irradiation (10, 20, 30, 50, 70, 90, and 110 Gy) at a dose rate of 55 Gy/min to induce the genetic variability for herb and oil yield as well as oil quality. A wide spectrum of variability for agro-morphological traits, herb yield, and quality profile was observed among the mutants.
The developed and selected superior mutants viz. MPK-5(1) and MPK-5(3) have a mean herb yield potential of 23.923 and 21.503 Kg/9m
; mean oil yield of 92.953 and 80.047 ml/plot; mean menthol content of 69.012% and 69.160% with mean menthofuran content of 1.554% and 0.531%, respectively.
Mutational breeding through γ- irradiation is considered complementary to the conventional breeding method, to broaden the spectrum of genetic variability. The developed and selected mutants namely viz. MPK-5(1) and MPK-5(3) identified as promising mutants, based on herb yield, oil yield, and essential oil quality, could be used as a parental line for exploitation in hybridization program/recombinant breeding.
Mutational breeding through γ- irradiation is considered complementary to the conventional breeding method, to broaden the spectrum of genetic variability. The developed and selected mutants namely viz. MPK-5(1) and MPK-5(3) identified as promising mutants, based on herb yield, oil yield, and essential oil quality, could be used as a parental line for exploitation in hybridization program/recombinant breeding.Although synaptic transmission in motor pathways can be regulated by neuromodulators, such as acetylcholine, few studies have examined how cholinergic activity affects cortical and spinal motor circuits following muscle contractions of varying intensities. This was a human, double-blinded, placebo-controlled, crossover study. Participants attended two sessions where they were administered either a placebo or 25 mg of promethazine. Electromyography of the abductor digiti minimi (ADM) was measured for all conditions. Motor evoked potentials (MEPs) were obtained via motor cortical transcranial magnetic stimulation (TMS), and F waves were obtained via ulnar nerve electrical stimulation. MEPs and F waves were examined 1) when the muscle was at rest; 2) after the muscle had been active; and 3) after the muscle had been fatigued. MEPs were unaffected by muscarinic receptor blockade when measurements were recorded from resting muscle or following a 50% isometric maximal voluntary contraction (MVC). However, muscarini blockade of muscarinic acetylcholine receptors enhances motor evoked potentials (elicited with transcranial magnetic stimulation) following strong muscle contractions, but not weak muscle contractions.The interconnection of the angular gyrus of right posterior parietal cortex (PPC) and the left motor cortex (LM1) is essential for goal-directed hand movements. Previous work with transcranial magnetic stimulation (TMS) showed that right PPC stimulation increases LM1 excitability, but right PPC followed by left PPC-LM1 stimulation (LPPC-LM1) inhibits LM1 corticospinal output compared with LPPC-LM1 alone. It is not clear if right PPC-mediated inhibition of LPPC-LM1 is due to inhibition of left PPC or to combined effects of right and left PPC stimulation on LM1 excitability. We used paired-pulse TMS to study the extent to which combined right and left PPC stimulation, targeting the angular gyri, influences LM1 excitability. We tested 16 healthy subjects in five paired-pulsed TMS experiments using MRI-guided neuronavigation to target the angular gyri within PPC. We tested the effects of different right angular gyrus (RAG) and LM1 stimulation intensities on the influence of RAG on LM1 and on influence of left angM1. Combined RAG and LAG stimulation increased GABAB, but not GABAA, receptor-mediated inhibition in left M1. These findings highlight unique brain interactions between the RAG and left M1.Individuals with motor incomplete spinal cord injuries (iSCI) often have impaired abilities to maintain upright balance. For able-bodied (AB) individuals, the ankle and hip joint accelerations are in antiphase to minimize the postural sway during quiet standing. Here we investigated how interjoint coordination between the ankle and hip joints was affected in individuals with iSCI, leading to their larger postural sway during quiet standing. Data from 16 individuals with iSCI, 14 age- and sex-matched AB individuals, and 13 young AB individuals were analyzed. The participants performed quiet standing during which kinematic and kinetic data were recorded. Postural sway was quantified using center-of-pressure velocity and center-of-mass acceleration. Individual ankle and hip joint kinematics were quantified, and the interjoint coordination was assessed using the cancellation index (CI), goal-equivalent variance (GEV), nongoal-equivalent variance (NGEV), and uncontrolled manifold (UCM) ratio. Individuals with iSCI joint accelerations. In addition, the ankle-hip coordination was equivalent between able-bodied individuals and those with motor incomplete spinal cord injury, which was not able to reduce the large body acceleration.Cilostazole (CLZ) is an anti-platelet drug that suffers from extensive first-pass metabolism and gastrointestinal side effects. This study aimed to prepare proniosomes for enhancing the transdermal delivery of CLZ to avoid its oral problems. proniosomes were prepared by a coacervation phase separation technique according to the D-optimal design to investigate the effect of formulation variables on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and the percent of the drug released after 2 and 24 h (Q2 and 24 h). The desirability criterion is set to select the optimum formula. The optimum formula(opt) with a desirability value (0.75), composed of 540 mg Span60 and 59.7 mg of cholesterol, had the highest EE% of (75.125 ± 0.125%), PS of (300.3 ± 0.2 nm), ZP of (-39.35 ± 0.15 mV), Q2h of (24.32 ± 0.13%) and Q24h of (81.175 ± 0.325%). Further, the opt-gel was prepared by using hydroxy propyl methyl cellulose (HPMC K4M). The opt-formula was subjected to an ex-vivo permeation study and showed a marked increase in drug flux of (22.89 ± 0.1 µg/cm2.h). The opt-gel was subjected to an in-vitro release study in comparison with the opt-formula that showed a more sustained release effect. The histopathological examination study confirmed the safety of the topical application of proniosomes. The CLZ-loaded proniosomes showed promising results with high potential to deliver it across the skin.
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