Hasil untuk "Biology"

Dipesh Singh Chuphal, Vimal Mishra

Abstract Reliable streamflow projections are essential for effective water‐resource management and climate adaptation. However, streamflow projections are associated with large uncertainties due to divergent precipitation projections from climate models, which directly propagate into hydrological estimates. Observation‐constrained approaches that condition future projections on past observations have been shown to reduce such uncertainties; however, they have not been applied to streamflow projections across the Indian rivers. Using long‐term streamflow and global mean surface temperature observations, climate model projections, hydrological modeling, and a Bayesian detection–attribution framework, we developed observational constrained streamflow projections for nine major Indian rivers. The method reduces the 5–95% confidence interval of future streamflow projections by nearly one‐third compared to raw multimodel ensembles, with constraint strength controlled by internal streamflow variability and inter‐model spread in the unconstrained ensemble. Projection uncertainty is further reduced to ∼20% when considering projections based only on skillful climate models. Constrained projections indicate significant increases in streamflow in the near‐, mid‐, and far‐future periods, except for the Cauvery basin, which shows a near‐term decline. Applying the method to raw precipitation projections reveals comparable constraint strength and increases confidence in the results, given the strong dependence of Indian river flows on precipitation. Our findings underscore the importance of combining skillful climate models with post‐processing constraint methods to substantially reduce model‐based uncertainty. Overall, our results provide critical insights into future streamflow changes across Indian rivers, supporting long‐term water‐resource planning and climate‐resilient management.

Società Italiana di Biologia Sperimentale

Nature-based compounds are increasingly investigated as eco-friendly tools to mitigate pollutant-induced toxicity in aquatic organisms, due to their richness in bioactive molecules (e.g., polyphenols, flavonoids, and other antioxidants) able to support cellular stress, immune competence, organisms’ resilience and homeostasis1. Beyond their biological potential, these approaches also fit a circular bioeconomy perspective, as they enable the valorisation of olive oil industry residues. Indeed, converting these low-value side streams into high-value extracts may reduce waste and promote sustainable innovation. Within this framework, the present investigation aimed to obtain novel insights into the potential protective and mitigatory role of the olive leaf extract (OLE), obtained from olive oil industry residual biomass, on the cellular and physiological performances of Mytilus galloprovincialis exposed to the neonicotinoid insecticide thiacloprid (THI), which is already recognised as a contaminant capable of compromising the health of organisms2. Bioactive molecules were obtained by solvent extraction of olive-derived residues, and the extract was then subjected to characterisation. Specimens were exposed to THI (4.5 μg/L), OLE (5 mg/L), and their mixture (THI+OLE), for fourteen days. Endpoints addressed immune competence, e.g., haemocyte functional activity and cytoskeleton-related signalling; cellular functionality and vitality, e.g., lysosomal stability and membrane integrity in haemocytes and digestive gland (DG) cells; redox balance through selected molecular biomarkers linked to antioxidant defences and cellular protection; cell osmoregulatory capacity through the evaluation the ability of DG cells to cope with osmotic challenge and restore cell volume. Results showed a consistent pattern across all analyses. No significant differences were observed between the control and OLE groups, whereas significant changes emerged in the THI-treated groups. Notably, co-exposure (THI+OLE) was associated with a recovery toward control-like levels. Overall, these findings support and provide novel insights into the potential of olive leaf-derived bioactive compounds to mitigate contaminant-induced toxicity, while highlighting the bioeconomic value of upgrading olive oil processing residues into functional extracts for environmentally sustainable applications in aquatic toxicology. In a broader “One Health” perspective, improving the resilience of marine bivalves contributes not only to ecosystem integrity but also to human well-being, considering the high commercial value of Mytilus galloprovincialis as a widely farmed and consumed seafood species and its central role in coastal economies and food supply chains.

Rafeeq P. H. Ahmed, Onur Kanisicak, Perwez Alam

<b>Background</b>: The limited regenerative capacity of adult mammalian cardiomyocytes (CMs) poses a significant challenge for cardiac repair following myocardial infarction. In contrast to adult mammals, CMs in zebrafish and newt hearts retain a lifelong capacity for proliferation and cardiac regeneration. Likewise, neonatal mice exhibit a brief postnatal period, during which CMs retain the ability to proliferate and contribute to myocardial repair, which markedly diminishes within the first week of life. Emerging evidence indicates that adult CM cell cycle progression is critically influenced by oxidative stress. Adult mammalian CMs possess a high mitochondrial content to meet their substantial energy demands. However, this also leads to elevated reactive oxygen species (ROS) production, resulting in DNA damage and subsequent cell cycle arrest. We hypothesize that reducing the mitochondrial content in adult CMs will mitigate ROS production, thereby facilitating cell cycle progression. <b>Methods</b>: Adult CMs were isolated from adult rats (≥12 weeks old). To induce mitophagy, adult CMs were transfected with parkin-expressing plasmid and then treated with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a mitochondrial protonophore, for 7 days. Post-treatment assessments included the quantification of adult CM proliferation, mitochondrial content, and ROS levels. <b>Results</b>: CCCP-treated adult CMs exhibited a significant increase in proliferation markers, including EdU incorporation, KI67, phospho-histone H3, and Aurora B. Furthermore, CCCP treatment significantly reduced the mitochondrial content, as evidenced by decreased MitoTracker, TMRM, and Tom20 staining compared to controls. This was accompanied by electron microscopy analysis, which showed a significant reduction in the mitochondrial number in the adult CM after CCCP treatment. Moreover, our results also demonstrate a marked reduction in oxidative stress, demonstrated by lower 123-dihydro-rhodamine (123-DHR), CellROX signals, and VDAC. <b>Conclusions</b>: Our findings demonstrate that CCCP-mediated mitochondrial depletion reduces oxidative stress and promotes cell cycle re-entry in adult CM. This study provides direct experimental evidence and substantiates the role of elevated mitochondria and ROS levels in adult CM cell cycle exit.

Ting Feng, Wenfeng Chen, Aja McDonagh et al.

Ian Jhemes Oliveira Sousa, Ian Jhemes Oliveira Sousa, Kerolayne de Melo Nogueira et al.

Waheed Ezzat, Khalid M. Mahrose, Ahmed M. Rizk et al.

The exploration for effective in-feed additives is growing owing to the global climatic change trend to alleviate the negative effects of heat stress in laying hens. This research assessed the potential of using B-glucan (G) as an antiheat stress agent in Matrouh laying hens subjected to early heat shock programs during the growing period. Factorial design (3 × 3) was used, including 3 levels of heat stress (control, heat shock at 3 d and at 3 d and 8 wk of age) and 3 levels of β-glucan (0, 100, and 200 mg β-glucan /kg diet). During the first 12 wk of egg production (EP), treatments were exposed to heat challenge. The results revealed that heat shock program applications at 3 d and 8 wk of age significantly decreased body weight at 36 wk of age (P < 0.05) and reduced (P < 0.05) feed intake (FI). While significantly (P < 0.05) improved feed conversion ratio (FCR), hemoglobin, RBCs, WBCs, immunoglobulin M (IgM), immunoglobulin G (IgG), and Heat shock protein (HSP70) of the Liver (P < 0.01) as compared with the control group. At the same time, there was a decrease in lymphocyte%, H/L ratio, cortisol, and T3 compared to the thermo-neutral control. When compared to the control group, hens fed a diet containing 200 mg of βG significantly (P < 0.05) improved body weight at 16 wk and final weight at 36 wk, feed conversion (FCR) (g. feed/g. egg mass), hen-day egg production, and egg mass, as well as the digestibility coefficients of crude protein (CP), dry matter (DM), metabolizable energy (ME), and cortisol. The interactions between heat chock programs and βG levels were nonsignificant for the most studied traits except daily feed intake. Therefore, the early heat shock exposure 2 times and supplementation of Β-glucan (βG) at 200 mg/kg diet during the growth period for laying hens that are exposed to heat stress during the reproductive period could improve productive, reproductive performance, HSP70 level and enhance immunity responses.

Na Kyung Lee, Woong Bi Jang, Dong Sik Seo et al.

Cardiovascular disease remains a global health concern. Stem cell therapy utilizing human cardiac progenitor cells (hCPCs) shows promise in treating cardiac vascular disease. However, limited availability and senescence of hCPCs hinder their widespread use. To address these challenges, researchers are exploring innovative approaches. In this study, a bioengineered cell culture plate was developed to mimic the natural cardiac tissue microenvironment. It was coated with a combination of extracellular matrix (ECM) peptide motifs and mussel adhesive protein (MAP). The selected ECM peptide motifs, derived from fibronectin and vitronectin, play crucial roles in hCPCs. Results revealed that the Fibro-P and Vitro-P coated plates significantly improved hCPC adhesion, proliferation, migration, and differentiation compared to uncoated plates. Additionally, long-term culture on the coated plates delayed cellular senescence and maintained hCPC stemness. These enhancements were attributed to the activation of integrin downstream signaling pathways. The findings suggest that the engineered ECM peptide motif-MAP-coated plates hold potential for enhancing the therapeutic efficacy of stem cell-based therapies in cardiac tissue engineering and regenerative medicine.

Stuart A. MacGowan, Fábio Madeira, Thiago Britto-Borges et al.

Abstract Protein evolution is constrained by structure and function, creating patterns in residue conservation that are routinely exploited to predict structure and other features. Similar constraints should affect variation across individuals, but it is only with the growth of human population sequencing that this has been tested at scale. Now, human population constraint has established applications in pathogenicity prediction, but it has not yet been explored for structural inference. Here, we map 2.4 million population variants to 5885 protein families and quantify residue-level constraint with a new Missense Enrichment Score (MES). Analysis of 61,214 structures from the PDB spanning 3661 families shows that missense depleted sites are enriched in buried residues or those involved in small-molecule or protein binding. MES is complementary to evolutionary conservation and a combined analysis allows a new classification of residues according to a conservation plane. This approach finds functional residues that are evolutionarily diverse, which can be related to specificity, as well as family-wide conserved sites that are critical for folding or function. We also find a possible contrast between lethal and non-lethal pathogenic sites, and a surprising clinical variant hot spot at a subset of missense enriched positions.

Irfa Anwar, Farheen Badrealam Khan, Sajid Maqsood et al.

Camel milk (CM) is known for its beneficial virtues in the human diet and health. This includes its antidiabetic properties demonstrated in many in vitro and in vivo studies. Nevertheless, the scientific rationale behind the molecular and cellular basis of such beneficial effects and the exact antidiabetic agent(s)/mechanism(s) are still elusive. In this review, we focused on the recent advances supporting the targeting of insulin receptor (IR) by CM components. Indeed, our recent work reported that CM proteins and derived peptides pharmacologically target IR in vitro leading to its activation and potentiation of insulin-mediated responses. The review describes the experimental approaches used to investigate the effects of CM on IR in vitro based on the fractionation of CM whey proteins to purify functional proteins and their hydrolysis by gastric proteases to generate bioactive peptides. In addition, we illustrated our cellular and molecular model consisting of studying the functional activity of CM fractions on IR and its downstream signaling pathways in the hepatocarcinoma (HepG2) and the human embryonic kidney (HEK293) cells using the bioluminescence resonance energy transfer (BRET), phosphorylation, and glucose uptake assays. Overall, our work demonstrated for the first time that CM lactoferrin and CM-derived bioactive peptides positively modulate IR and its related signaling pathways in HepG2 and HEK293 cells. As a conclusion, the pharmacological targeting of IR by CM sheds more light on the antidiabetic properties of CM by providing its molecular basis that may constitute a solid rationale for the development of new generation of antidiabetic tools from CM-derived proteins and peptides and the utilization of CM in the management of diabetes. The sequencing and the synthesis of the potent bioactive CM peptides may open promising perspectives for their application as antidiabetic agents.

Yingjie Wang, Lulu Wang, Fuli Hu et al.

High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. <i>Mycoplasma gallisepticum</i> (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.

Saul Vislei Simões da Silva, Orlando Maia Barboza, Jéssica Teles Souza et al.

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, ¹H and ¹³C NMR spectra. The antioxidant potential was evaluated against the radical ABTS^•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (<i>p</i> < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC₅₀ > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC₅₀ = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

V. HÝSKOVÁ, K. BĚLONOŽNÍKOVÁ, N. ČEŘOVSKÁ et al.

Heat shock and almost all types of stresses associated with oxidative stress are accompanied by heat shock protein (HSP) expression. HSPs are involved in refolding denatured proteins and directing unrepairable proteins for degradation. Thus, under stress conditions, HSPs help to restore cellular balance. However, in virus-infected plants, HSP70 can have both positive and negative effects because viruses usually recruit HSP70. HSP70 can promote the replication and translation of the viral genome, the formation of viral replication complexes, and the propagation of viral particles from cell to cell and throughout the plant. HSP gene silencing in various virus-host plants systems and the comparison of susceptible and resistant species have shown that HSPs70 accelerate the development of infection. Conversely, during the process known as thermotherapy, the temperature increase inhibits viral replication in some host and virus systems. The success of thermotherapy depends not only on the temperature and treatment period or duration but also on the plant species and viral strain. In this review, we discuss the ambiguous role that HSPs70 play during viral infections in plants towards weighing the balance between their positive and negative functions.

Michael Gross

Ian M. Hastings, Diggory Hardy, Katherine Kay et al.

Abstract Introduction Control strategies for human infections are often investigated using individual‐based models (IBMs) to quantify their impact in terms of mortality, morbidity and impact on transmission. Genetic selection can be incorporated into the IBMs to track the spread of mutations whose origin and spread are driven by the intervention and which subsequently undermine the control strategy; typical examples are mutations which encode drug resistance or diagnosis‐ or vaccine‐escape phenotypes. Methods and results We simulated the spread of malaria drug resistance using the IBM OpenMalaria to investigate how the finite sizes of IBMs require strategies to optimally incorporate genetic selection. We make four recommendations. Firstly, calculate and report the selection coefficients, s, of the advantageous allele as the key genetic parameter. Secondly, use these values of “s” to calculate the wait time until a mutation successfully establishes itself in the pathogen population. Thirdly, identify the inherent limits of the IBM to robustly estimate small selection coefficients. Fourthly, optimize computational efficacy: when “s” is small, fewer replicates of larger IBMs may be more efficient than a larger number of replicates of smaller size. Discussion The OpenMalaria IBM of malaria was an exemplar and the same principles apply to IBMs of other diseases.

Liu Y, Song X, Wu M et al.

Yusi Liu, Xue Song, Moli Wu, Jiao Wu, Jia Liu Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People&rsquo;s Republic of ChinaCorrespondence: Jia LiuLiaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, People&rsquo;s Republic of ChinaTel +86-411-86110318Email lj0330lj@163.comPurpose: Temozolomide (TMZ) is a commonly used anti-glioblastoma (GBM) drug. However, glioblastoma cells frequently show primary and acquired resistance to TMZ. As a promising anti-GBM candidate, resveratrol (Res) faces the similar problem as TMZ. Although resveratrol combined with TMZ (Res/TMZ) has been reported to be used to treat GBMs, it remains unclear whether this combination is broad-spectrum for all glioma cells until now, especially for GBM cells/cases with dual drug resistance. The study aimed to evaluate the synergistic effects of resveratrol and TMZ against GBMs and identify the underlying mechanisms.Materials and Methods: Drug sensitivities of rat RG-2, human LN-18 and LN-428 cell lines and effectiveness of Res/TMZ combinations were investigated via multiple experimental methods. O6-methylguanine-DNA methyltransferase (MGMT) was observed by Western blotting and immunocytochemistry (ICC). Transducer and activator of transcription 3 (STAT3) signaling pathway and expression changes of STAT3-related gene were detected to explore the possible synergistic mechanism.Results: One hundred micromolar resveratrol and 500 &mu;M TMZ inhibited the growth of RG-2 cells and the low-dose combination (25 &mu;M/250 &mu;M) showed similar suppressive effects. LN-18 and, especially, LN-428 cells were neither sensitive to 100 &mu;M resveratrol nor to 500 &mu;M TMZ, while their growth was suppressed by combination of 75 &mu;M Res/750 &mu;M TMZ with the suppressive rates of 62.5% and 28.6% and apoptosis rates of 11.9% and 7.4%, respectively. Resveratrol had regulatory effect on the expression of MGMT and it could significantly down-regulate MGMT overexpression caused by TMZ. In addition, STAT3/Bcl-2/survivin signaling pathway was also remarkably inhibited in Res/TMZ-treated GBM cells.Conclusion: Our results demonstrated synergistic effects of Res/TMZ on RG-2 cells and their bilaterally sensitizing effects to LN-18 and LN-428 cells. Frequent upregulation of MGMT and activation of STAT3 are the unfavorable factors for the treatment of GBMs and they may be the potential targets of Res/TMZ therapy.Keywords: resveratrol, temozolomide, synergistic effects, glioblastoma, MGMT, STAT3, Bcl-2, survivin