Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly ...in the context of the COVID-19 pandemic. The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods. We analyzed data from 15,381 patients tested for RSV between 2017 and 2023. Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses. Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.
Proteasomes are known to degrade proteins involved in various processes like metabolism, signal transduction, cell-cycle regulation, inflammation, and apoptosis. Evidence showed that protein ...degradation has a strong influence on developing neurons as well as synaptic plasticity. Here, we have shown that sulforaphane (SFN) could prevent the deleterious effects of postnatal proteasomal inhibition on spatial reference and working memory of adult mice. One day old Balb/c mice received intracerebroventricular injections of MG132 and SFN. Sham received an equal volume of aCSF. We observed that SFN pre-administration could attenuate MG132 mediated decrease in proteasome and calpain activities. In vitro findings revealed that SFN could induce proteasomal activity by enhancing the expression of catalytic subunit-β5. SFN pre-administration prevented the hippocampus based spatial memory impairments during adulthood, mediated by postnatal MG132 exposure. Histological examination showed deleterious effects of MG132 on pyramidal neurons and granule cell neurons in DG and CA3 sub-regions respectively. Furthermore, SFN pre-administration has shown to attenuate the effect of MG132 on proteasome subunit-β5 expression and also induce the Nrf2 nuclear translocation. In addition, SFN pre-administered mice have also shown to induce expression of pCaMKII, pCreb, and mature/pro-Bdnf, molecules which play a crucial role in spatial learning and memory consolidation. Our findings have shown that proteasomes play an important role in hippocampal synaptic plasticity during the early postnatal period and SFN pre-administration could enhance the proteasomal activity as well as improve spatial learning and memory consolidation.
•Postnatal MG132 administration reduced the proteasome and calpain activities.•Defected postnatal proteasome could promote Aβ accumulation in hippocampal cells.•Postnatal proteasome inhibition ...impaired spatial memory in adult mice.
Ubiquitin-proteasome system (UPS) has emerged as major molecular mechanism which modulates synaptic plasticity. However, very little is known about what happens if this system fails during postnatal brain development. In the present study, MG132 was administered intracerebroventricularly in BALB/c mice pups at postnatal day one (P1), a very crucial period for synaptogenesis. Both 20S proteasome and calpain activities were found to be reduced in the mid brain of MG132-administered pups after 24 h. Mice (P40) which received MG132 on P1 were subjected to Morris water maze (MWM) training. Analysis showed spatial learning and memory of MG132 mice was significantly impaired when compared to age-matched controls. Hematoxylin and eosin as well as Cresyl Violet staining revealed substantial loss of cellular connections, distorted architecture and increased pyknosis in hippocampal CA1 and CA3 regions of MG132 mice. Immunohistochemical analysis of MG132 mice showed increased accumulation of intracellular amyloid-β in hippocampal cells when compared to control. Moreover, double immunostaining revealed increased expression of amyloid precursor protein C-terminal fragments (APP-CTFβ) without affecting β-secretase expression in MG132 mice. Real-Time PCR analyses showed significant increase in hippocampal expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate A1 (GluA1), but no change in the brain-derived neurotrophic factor (Bdnf) expression in MG132 mice. Western blot analyses showed decreased levels of pThr286-CaMKIIα:CaMKIIα and pSer133-CREB:CREB ratio but increased pro:mature BDNF ratio in the hippocampus of MG132 mice. Taken together, postnatal proteasome inhibition could lead to accumulation of intracellular amyloid-β protein aggregates, which mediate hippocampus-dependent spatial memory impairments in adult mice.
Microglia play an important role in synaptic pruning and controlled phagocytosis of neuronal cells during developmental stages. However, the mechanisms that regulate these functions are not ...completely understood. The present study was designed to investigate the role of purinergic signalling in microglial migration and phagocytic activity during post-natal brain development. One-day-old BALB/c mice received lipopolysaccharide (LPS) and/or a purinergic analogue (2-methylthioladenosine-5′-diphosphate; 2MeSADP), intracerebroventrically (i.c.v.). Combined administration of LPS and 2MeSADP resulted in activation of microglia as evident from increased expression of ionised calcium-binding adapter molecule 1 (Iba1). Activated microglia showed increased expression of purinergic receptors (P2Y
2
, P2Y
6
and P2Y
12
). LPS either alone or in combination with 2MeSADP induced the expression of Na
+
/Ca
2+
exchanger (NCX-1) and P/Q-type Ca
2+
channels along with MARCKS-related protein (MRP), which is an integral component of cell migration machinery. In addition, LPS and 2MeSADP administration induced the expression of microglial CD11b and DAP12 (DNAX-activation protein 12), which are known to be involved in phagocytosis of neurons during development. Interestingly, administration of thapsigargin (TG), a specific Ca
2+
-ATPase inhibitor of endoplasmic reticulum, prevented the LPS/2MeSADP-induced microglial activation and migration by down-regulating the expression of Iba1 and MRP, respectively. Moreover, TG also reduced the LPS/2MeSADP-induced expression of CD11b/DAP12. Taken together, the findings reveal for the first time that Ca
2+
-mediated purinergic receptors regulate the migration and phagocytic ability of microglia during post-natal brain development.
Plant responses to drought are mediated by hormones like ABA (abscisic acid) and auxin. These hormones regulate plant drought responses by modulating various physiological and biological processes ...via cell signaling. ABA accumulation and signaling are central to plant drought responses. Auxin also regulates plant adaptive responses to drought, especially via signal transduction mediated by the interaction between ABA and auxin. In this review, we explored the interactive roles of ABA and auxin in the modulation of stomatal movement, root traits and accumulation of reactive oxygen species associated with drought tolerance.
•ABA and auxin interaction modulates stomata-mediated water loss under drought.•Interaction between ABA and auxin influences water uptake mechanism under drought.•An intricate relationship among ROS, ABA and auxin fine-tunes drought responses.
Double-stranded RNA (dsRNAs) molecules are the precursors and effective triggers of RNAi in most organisms. RNAi can be induced by the direct introduction of dsRNAs in plants, fungi, insects, and ...nematodes. Until now RNAi is usually established by transformation of the plant with a construct that produces hairpin RNAs. Alternatively, advances in RNA biology demonstrated efficiently the in vitro method of large-scale synthesis of dsRNA molecule. Here we describe the de novo synthesis of dsRNA molecule targeting the specific gene of interest for functional application. Selection of off-target effective siRNA regions, flanking of T7 promoter sequences, T7 polymerase reaction, and maintenance of the stability of dsRNA molecules are the main criteria of this method to obtain pure and effective yield for functional applications. IPTG (isopropyl-β-D-thiogalactopyranoside) induced, T7 express E. coli cells, could be used for large scale synthesis of dsRNA molecule are also described in this method.
Wound is the major health problem associated with skin damages and arises because of various types of topical injuries. Furthermore, wounds in patients with diabetes take a relatively long time to ...heal. Currently, herbal medicines have been extensively used for wound care and management. Here, we engineered polymeric hybrid hydrogel of dimethylaminoethyl acrylate and hyaluronic acid (pDMAEMA–HA), which was impregnated with a herbal extract of Didymocarpus pedicellatus. The developed polymeric hybrid hydrogel system can be used for effective therapy of incurable wounds. Therefore, the development of D. pedicellatus-impregnated pDMAEMA–HA (pDPi-DMAEMA–HA) hybrid hydrogel was accomplished by the synthesis of pDMAEMA–HA hydrogel via the optimization of various reaction parameters followed by impregnation of herbal drugs D. pedicellatus. The developed hydrogel composite was well characterized via various techniques, and swelling kinetics was performed to analyze the water uptake property. The swelling ratio was found to be 1600% in both types of hydrogels. To evaluate the wound healing of these polymeric hydrogels, the Wistar rats full-thickness excision wound model was utilized. The healing strength of hydrogels was determined using measurement of wound contraction and histopathological study. The results of wound healing by these polymeric hydrogels revealed that animals treated with the pDPi-DMAEMA–HA hybrid hydrogel group were found to have a higher level of wound closure as compared to marketed formulation as well as polymeric hybrid hydrogel. The histopathologic examinations implied that pDPi-DMAEMA–HA hybrid hydrogel and polymeric hybrid hydrogel-treated groups exhibited enhanced cutaneous wound repair as well as high level of cellular repair and maintenance compared to the standard group because of hyaluronic acid roles in various stages of wound repair.
Plants modulate the metabolism of phytohormones and their signaling pathways under drought to regulate physiological and adaptive responses. Jasmonic acid (JA) is one of the major classes of ...phytohormones and has been found to potentially enhance plant tolerance to various abiotic stresses, including drought. The JASMONATE ZINC FINGER INFLORESCENCE MERISTEM (ZIM)-DOMAIN (JAZ) proteins are the negative regulators in the JA-signaling pathway. The JAZ protein family is explicit to plants and involved in the regulation of numerous biological processes, including drought-responsive mechanisms. In this review, we synthesize the mechanistic insight into the roles of JAZ proteins in the regulation of drought responses by connecting the JA-signaling with abscisic acid-signaling.
PDF