Aging is a normal human cycle and the most important risk factor for neurodegenerative diseases. Alternations in cells due to aging contribute to loss of the nutrient-sensing, cell function, ...increased oxidative stress, loss of the homeostasis cell, genomic instability, the build-up of malfunctioning proteins, weakened cellular defenses, and a telomere split. Disturbance of these essential cellular processes in neuronal cells can lead to life threats including Alzheimer's disease (AD), Huntington's disease (HD), Lewy's disease, etc. The most common cause of death in the elderly population is AD. Specific therapeutic molecules were created to alleviate AD's social, economic, and health burden. In clinical practice, almost every chemical compound was found to relieve symptoms only in palliative treatment. The reason behind these perfect medicines is that the current medicines are not effective in targeting the cause of this disease. In this paper, we explored the potential role of flavonoid and polyphenolic compounds, which could be the most effective preventative anti-Alzheimer's strategy.
cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential ...gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to
-acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.
Aging is an important stage of the human life cycle and the primary risk factor for Neurodegenerative Diseases (ND). The aging process contributes to modifications in cells, which may lead to a lack ...of nutrient signaling, disrupted cellular activity, increased oxidative pressure, cell homeostasis depletion, genomic instability, misfolded protein aggregation, impaired cellular protection, and telomere reduction. The neuropathologies found in Alzheimer's Disease (AD) and Parkinson's Disease (PD) are internally and extrinsically compound environmental stressors which may be partially alleviated by using different phytochemicals. The new therapies for ND are restricted as they are primarily targeted at final disease progression, including behavioral shifts, neurological disorders, proteinopathies and neuronal failure. This review presents the role of phytochemicals-related polyphenolic compounds as an accompanying therapy model to avoid neuropathologies linked to AD, PD and to simultaneously enhance two stochastic stressors, namely inflammation and oxidative stress, promoting their disease pathologies. Therefore, this approach represents a prophylactic way to target risk factors that rely on their action against ND that does not occur through current pharmacological agents over the life of a person.
COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has ...necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.
Sediment samples were collected from ten selected sites of the lower Meghna River estuary, and six heavy metals were analyzed with Atomic Absorption Spectrophotometry (AAS) to assess the ...contamination level and the metals’ association with sediment grain size. The current results revealed that the mean concentrations of the studied metals were ranked in descending order of iron (Fe) (1.29 × 103 mg/kg) > zinc (Zn) (42.41 mg/kg) > lead (Pb) (12.48 mg/kg) > chromium (Cr) (10.59 mg/kg) > copper (Cu) (6.22 mg/kg) > cadmium (Cd) (0.28 mg/kg). The geo-accumulation, contamination, and pollution load indexes suggested that the lower Meghna river estuary was not contaminated by Fe, Zn, Pb, Cr, and Cu. The mean size of the sediment ranged from 28.92 to 126.2 μm, and the Pearson correlation coefficient showed a significant association between Fe and Pb (coefficient of determination, r2 = 0.836; p < 0.05), and no significant correlation was found between individual metals and grain size, indicating no or low influence on the metals distribution.
Staphylococcus aureus is a notorious biofilm-producing pathogen that is frequently isolated from implantable medical device infections. As biofilm ages, it becomes more tolerant to antimicrobial ...treatment leading to treatment failure and necessitating the costly removal of infected devices. In this study, we performed in-solution digestion followed by TMT-based high-throughput mass spectrometry and investigated what changes occur in the proteome of S. aureus biofilm grown for 3-days and 12-days in comparison with 24 h planktonic. It showed that proteins associated with biosynthetic processes, ABC transporter pathway, virulence proteins, and shikimate kinase pathway were significantly upregulated in a 3-day biofilm, while proteins associated with sugar transporter, degradation, and stress response were downregulated. Interestingly, in a 3-day biofilm, we observed numerous proteins involved in the central metabolism pathways which could lead to biofilm growth under diverse environments by providing an alternative metabolic route to utilize energy. In 12-day biofilms, proteins associated with peptidoglycan biosynthesis, sugar transporters, and stress responses were upregulated, whereas proteins associated with ABC transporters, DNA replication, and adhesion proteins were downregulated. Gene Ontology analysis revealed that more proteins are involved in metabolic processes in 3dwb compared with 12dwb. Furthermore, we observed significant variations in the formation of biofilms resulting from changes in the level of metabolic activity in the different growth modes of biofilms that could be a significant factor in S. aureus biofilm maturation and persistence. Collectively, potential marker proteins were identified and further characterized to understand their exact role in S. aureus biofilm development, which may shed light on possible new therapeutic regimes in the treatment of biofilm-related implant-associated infections.
The Gram-positive bacterium
is responsible for serious acute and chronic infections worldwide and is well-known for its biofilm formation ability. Recent findings of biofilms on dry hospital surfaces ...emphasise the failures in current cleaning practices and disinfection and the difficulty in removing these dry surface biofilms (DSBs). Many aspects of the formation of complex DSB biology on environmental surfaces in healthcare settings remains limited. In the present study, we aimed to determine how the protein component varied between DSBs and traditional hydrated biofilm. To do this, biofilms were grown in tryptic soy broth (TSB) on removable polycarbonate coupons in the CDC biofilm reactor over 12 days. Hydrated biofilm (50% TSB for 48 h, the media was then changed every 48 h with 20% TSB, at 37 °C with 130 rpm). DSB biofilm was produced in 5% TSB for 48 h at 35 °C followed by extended periods of dehydration (48, 66, 42 and 66 h at room temperature) interspersed with 6 h of 5% TSB at 35 °C. Then, we constructed a comprehensive reference map of 12-day DSB and 12-day hydrated biofilm associated proteins of
using a high-throughput tandem mass tag (TMT)-based mass spectrometry. Further pathway analysis of significantly differentially expressed identified proteins revealed that proteins significantly upregulated in 12-day DSB include PTS glucose transporter subunit IIBC (PtaA), UDP-N-acetylmuramate-L-alanine ligase (MurC) and UDP-N-acetylenolpyruvoylglucosamine (MurB) compared to 12-day hydrated biofilm. These three proteins are all linked with peptidoglycan biosynthesis pathway and are responsible for cell-wall formation and thicker EPS matrix deposition. Increased cell-wall formation may contribute to the persistence of DSB on dry surfaces. In contrast, proteins associated with energy metabolisms such as phosphoribosyl transferase (PyrR), glucosamine--fructose-6-phosphate aminotransferase (GlmS), galactose-6-phosphate isomerase (LacA), and argininosuccinate synthase (ArgG) were significantly upregulated whereas ribosomal and ABC transporters were significantly downregulated in the 12-day hydrated biofilm compared to DSB. However, validation by qPCR analysis showed that the levels of gene expression identified were only partially in line with our TMT-MS quantitation analysis. For the first time, a TMT-based proteomics study with DSB has shed novel insights and provided a basis for the identification and study of significant pathways vital for biofilm biology in this reference microorganism.
Sulphur plays a vital role in the formation and biosynthesis of protein, chlorophyll, and few amino acids. To investigate the effect of sulphur fertilizer on leaf biomass yield, critical sulphur ...concentration, sulphur requirement and uptake by Aloe vera L., a pot experiment was carried out following completely randomized design with six levels of sulphur viz., 0, 15, 30, 45, 60 and 80 kg ha−1 with three replications. The results of the study revealed that the growth attributes, leaf and gel yield, and sulphur uptake significantly improved with sulphur application and the best results were obtained from the application of 45 kg sulphur ha−1. On average, addition of sulphur enhanced the leaf biomass yield by 47.5% and sulphur use efficiency by 38% compared to control. The effect of sulphur on the growth parameters and their significant and positive correlations with yield signifies the importance of sulphur on the yield and quality of A. vera. The calculated minimum amount of sulphur for 80% leaf biomass production was 21.1 kg sulphur ha−1 with a critical leaf sulphur concentration of 0.23% in A. vera. Moreover, sulphur addition to soil substantially enhanced the economic returns of A. vera. Therefore, addition of 45 kg sulphur ha−1 could be a better option for obtaining higher yield and economic return of A. vera.
Aloe vera L.; Leaf yield; Sulphur use efficiency; Critical sulphur concentration; Sulphur requirement; Agricultural policy; Agricultural soil science; Agricultural technology; Agronomy; Soil science
This study aims to investigate the potential analgesic properties of the crude extract of
leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a ...moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (**
< 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter-connected. Therefore, multiple inflammatory modulator proteins were selected as the target for in silico analysis. Computational analysis suggests that all the selected targets had different degrees of interaction with the phytochemicals from the extract. Rutin (RU), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA) could regulate multiple targets with a robust efficiency. None of the compounds showed selectivity to Cyclooxygenase-2 (COX-2). However, regulation of COX and lipoxygenase (LOX) cascade by PA can reduce non-steroidal analgesic drugs (NSAIDs)-related side effects, including asthma. RU showed robust regulation of cytokine-mediated pathways like RAS/MAPK and PI3K/NF-kB by inhibition of EGFR and IKBα (IKK), which may prevent multi-organ failure due to cytokine storm in several microbial infections, for example, SARS-CoV-2. Further investigation, using in vivo and in vitro experiments, can be conducted to develop multi-target anti-inflammatory drugs using the isolated compounds from the extract.
The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells ...targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection.
In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2).
The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses.
These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.
PDF
