Recent advancements in the understanding of how sperm develop into offspring have shown complex interactions between environmental influences and genetic factors. The past decade, marked by a research surge, has not only highlighted the profound impact of paternal contributions on fertility and reproductive outcomes but also revolutionized our comprehension by unveiling how parental factors sculpt traits in successive generations through mechanisms that extend beyond traditional inheritance patterns. Studies have shown that offspring are more susceptible to environmental factors, especially during critical phases of growth. While these factors are broadly detrimental to health, their effects are especially acute during these periods. Moving beyond the immutable nature of the genome, the epigenetic profile of cells emerges as a dynamic architecture. This flexibility renders it susceptible to environmental disruptions. The primary objective of this review is to shed light on the diverse processes through which environmental agents affect male reproductive capacity. Additionally, it explores the consequences of paternal environmental interactions, demonstrating how interactions can reverberate in the offspring. It encompasses direct genetic changes as well as a broad spectrum of epigenetic adaptations. By consolidating current empirically supported research, it offers an exhaustive perspective on the interwoven trajectories of the environment, genetics, and epigenetics in the elaborate transition from sperm to offspring.
Sponges are aquatic, spineless organisms that belong to the phylum Porifera. They come in three primary classes: Hexactinellidae, Demospongiae, and Calcarea. The Demospongiae class is the most dominant, making up over 90% of sponge species. One of the most widely studied genera within the Demospongiae class is Xestospongia, which is found across Southeast Asian waters. This genus is of particular interest due to the production of numerous primary and secondary metabolites with a wide range of biological potentials. In the current review, the antioxidant, anticancer, anti-inflammatory, antibacterial, antiviral, antiparasitic, and cytotoxic properties of metabolites from several varieties of Southeast Asian Xestospongia spp. were discussed. A total of 40 metabolites of various natures, including alkaloids, fatty acids, steroids, and quinones, were highlighted in X. bergquistia, X. testudinaria, X. muta, X. exigua, X. ashmorica and X. vansoesti. The review aimed to display the bioactivity of Xestospongia metabolites and their potential for use in the pharmaceutical sector. Further research is needed to fully understand their bioactivities.
Corneal diseases are the most common eye disorders. Deep learning techniques are used to perform automated diagnoses of cornea. Deep learning networks require large-scale annotated datasets, which is conceded as a weakness of deep learning. In this work, a method for synthesizing medical images using conditional generative adversarial networks (CGANs), is presented. It also illustrates how produced medical images may be utilized to enrich medical data, improve clinical decisions, and boost the performance of the conventional neural network (CNN) for medical image diagnosis. The study includes using corneal topography captured using a Pentacam device from patients with corneal diseases. The dataset contained 3448 different corneal images. Furthermore, it shows how an unbalanced dataset affects the performance of classifiers, where the data are balanced using the resampling approach. Finally, the results obtained from CNN networks trained on the balanced dataset are compared to those obtained from CNN networks trained on the imbalanced dataset. For performance, the system estimated the diagnosis accuracy, precision, and F1-score metrics. Lastly, some generated images were shown to an expert for evaluation and to see how well experts could identify the type of image and its condition. The expert recognized the image as useful for medical diagnosis and for determining the severity class according to the shape and values, by generating images based on real cases that could be used as new different stages of illness between healthy and unhealthy patients.
Information technology has become an integral aspect of the drug development process. The virtual screening process (VS) is a computational technique for screening chemical compounds in a reasonable amount of time and cost. The similarity search is one of the primary tasks in VS that estimates a molecule's similarity. It is predicated on the idea that molecules with similar structures may also have similar activities. Many techniques for comparing the biological similarity between a target compound and each compound in the database have been established. Although the approaches have a strong performance, particularly when dealing with molecules with homogenous active structural, they are not enough good when dealing with structurally heterogeneous compounds. The previous works examined many deep learning methods in the enhanced Siamese similarity model and demonstrated that the Enhanced Siamese Multi-Layer Perceptron similarity model (SMLP) and the Siamese Convolutional Neural Network-one dimension similarity model (SCNN1D) have good outcomes when dealing with structurally heterogeneous molecules. To further improve the retrieval effectiveness of the similarity model, we incorporate the best two models in one hybrid model. The reason is that each method gives good results in some classes, so combining them in one hybrid model may improve the retrieval recall. Many designs of the hybrid models will be tested in this study. Several experiments on real-world data sets were conducted, and the findings demonstrated that the new approaches outperformed the previous method.
Date palm (Phoenix dactylifera L.) is an essential agricultural crop in most Middle Eastern countries, and its fruit, known as dates, is consumed by millions of people. Date seeds, a by-product of the date fruit processing industry, are a waste product used as food for domestic farm animals. Date seeds contain abundant sources of carbohydrates, oil, dietary fiber, and protein; they also contain bioactive phenolic compounds that may possess potential biological properties. In addition, its rich chemical composition makes date seeds suitable for use in food product formulation, cosmetics, and medicinal supplements. This review aims to provide a discourse on the nutritional value of date seeds. The latest data on the cytotoxicity of date seed compounds against cancer cell lines, its ability to combat diabetes, antioxidant potential, antimicrobial effect, and anti-inflammatory activity will be provided, considering its potential to be a nutritional therapeutic agent for chronic diseases. Application of date seeds in the form of powder and oil will also be discussed.
Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.
The diagnostic value of coronary computed tomography angiography (CCTA) is significantly affected by high calcification in the coronary arteries owing to blooming artifacts limiting its accuracy in assessing the calcified plaques. This study aimed to simulate highly calcified plaques in 3D-printed coronary models. A combination of silicone + 32.8% calcium carbonate was found to produce 800 HU, representing extensive calcification. Six patient-specific coronary artery models were printed using the photosensitive polyurethane resin and a total of 22 calcified plaques with diameters ranging from 1 to 4 mm were inserted into different segments of these 3D-printed coronary models. The coronary models were scanned on a 192-slice CT scanner with 70 kV, pitch of 1.4, and slice thickness of 1 mm. Plaque attenuation was measured between 1100 and 1400 HU. Both maximum-intensity projection (MIP) and volume rendering (VR) images (wide and narrow window widths) were generated for measuring the diameters of these calcified plaques. An overestimation of plaque diameters was noticed on both MIP and VR images, with measurements on the MIP images close to those of the actual plaque sizes (<10% deviation), and a large measurement discrepancy observed on the VR images (up to 50% overestimation). This study proves the feasibility of simulating extensive calcification in coronary arteries using a 3D printing technique to develop calcified plaques and generate 3D-printed coronary models.
Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson's disease (PD). Lipophilic tanshinones are major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins and the inhibition of MAO-A. Since MAO-B inhibition is considered an effective therapeutic strategy for PD, we tested the inhibitory activities of three abundant tanshinone congeners against recombinant human MAO (hMAO) isoenzymes through in vitro experiments. In our study, tanshinone I (1) exhibited the highest potency against hMAO-A, followed by tanshinone IIA and cryptotanshinone, with an IC50 less than 10 µM. They also suppressed hMAO-B activity, with an IC50 below 25 µM. Although tanshinones are known to inhibit hMAO-A, their enzyme inhibition mechanism and binding sites have yet to be investigated. Enzyme kinetics and molecular docking studies have revealed the mode of inhibition and interactions of tanshinones during enzyme inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological targets of 1, and in vitro functional assays confirmed the selective M4 antagonist nature of 1 (56.1% ± 2.40% inhibition of control agonist response at 100 µM). These findings indicate that 1 is a potential therapeutic molecule for managing the motor dysfunction and depression associated with PD.
The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.
The use of seaweeds as additives in animal nutrition may be a valid option to traditional feed as they represent a rich source of minerals, carbohydrates and antioxidants. The aim of this study was to analyze the chemical composition and in vitro antioxidant capacity of two tropical eucheumatoids, Kappaphycus alvarezii and Kappaphycus striatus, in Malaysian wild offshore waters. The chemical analysis was performed via inductively coupled plasma-optical emission spectroscopy for evaluating the concentration of toxic (Cd, Pb, Hg, As) and essential elements (Mn, Fe, Cu, Ni, Zn, Se); NMR spectroscopy was used for carrageenans investigation. Furthermore, the soluble and fat-soluble antioxidant capacities were determined by FRAP, DPPH and ABTS assays. The chemical analysis revealed a higher content of trace elements in K. alvarezii as compared to K. striatus, and both exhibited a high mineral content. No significant differences in metal concentrations were found between the two species. Both samples showed a mixture of prevailing κ- and t-carrageenans. Finally, the levels of soluble and fat-soluble antioxidants in K. alvarezii were significantly higher than in K. striatus. Our findings suggest that K. alvarezii could be used as a potential feed additive because of its favorable chemical and nutritional features.
This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.
Plants are rich in phytoconstituent biomolecules that served as a good source of medicine. More recently, they have been employed in synthesizing metal/metal oxide nanoparticles (NPs) due to their capping and reducing properties. This green synthesis approach is environmentally friendly and allows the production of the desired NPs in different sizes and shapes by manipulating parameters during the synthesis process. The most commonly used metals and oxides are gold (Au), silver (Ag), and copper (Cu). Among these, Cu is a relatively low-cost metal that is more cost-effective than Au and Ag. In this review, we present an overview and current update of plant-mediated Cu/copper oxide (CuO) NPs, including their synthesis, medicinal applications, and mechanisms. Furthermore, the toxic effects of these NPs and their efficacy compared to commercial NPs are reviewed. This review provides an insight into the potential of developing plant-based Cu/CuO NPs as a therapeutic agent for various diseases in the future.
Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.
Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords "Catalpol", "Type 1 diabetes mellitus", "Type 2 diabetes mellitus", and "diabetic complications". Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.
As the most recognizable natural secondary carotenoid astaxanthin producer, the green microalga Haematococcus pluvialis cultivation is performed via a two-stage process. The first is dedicated to biomass accumulation under growth-favoring conditions (green stage), and the second stage is for astaxanthin evolution under various stress conditions (red stage). This mini-review discusses the further improvement made on astaxanthin production by providing an overview of recent works on H. pluvialis, including the valuable ideas for bioprocess optimization on cell growth, and the current stress-exerting strategies for astaxanthin pigment production. The effects of nutrient constituents, especially nitrogen and carbon sources, and illumination intensity are emphasized during the green stage. On the other hand, the significance of the nitrogen depletion strategy and other exogenous factors comprising salinity, illumination, and temperature are considered for the astaxanthin inducement during the red stage. In short, any factor that interferes with the cellular processes that limit the growth or photosynthesis in the green stage could trigger the encystment process and astaxanthin formation during the red stage. This review provides an insight regarding the parameters involved in bioprocess optimization for high-value astaxanthin biosynthesis from H. pluvialis.
Continuously increasing energy demand and growing concern about energy resources has attracted much research in the field of clean and sustainable energy sources. In this context, zero-emission fuels are required for energy production to reduce the usage of fossil fuel resources. Here, we present the synthesis of Pd-Ag-decorated reduced graphene oxide (rGO) nanostructures using a green chemical approach with stevia extract for hydrogen production and antibacterial studies under light irradiation. Moreover, bimetallic nanostructures are potentially lime lighted due to their synergetic effect in both scientific and technical aspects. Structural characteristics such as crystal structure and morphological features of the synthesized nanostructures were analyzed using X-ray diffraction and transmission electron microscopy. Analysis of elemental composition and oxidation states was carried out by X-ray photoelectron spectroscopy. Optical characteristics of the biosynthesized nanostructures were obtained by UV-Vis absorption spectroscopy, and Fourier transform infrared spectroscopy was used to investigate possible functional groups that act as reducing and capping agents. The antimicrobial activity of the biosynthesized Pd-Ag-decorated rGO nanostructures was excellent, inactivating 96% of Escherichia coli cells during experiments over 150 min under visible light irradiation. Hence, these biosynthesized Pd-Ag-decorated rGO nanostructures can be utilized for alternative nanomaterial-based drug development in the future.
Heliotropium is one of the most important plant genera to have conventional folklore importance, and hence is a potential source of bioactive compounds. Thus, the present study was designed to explore the therapeutic potential of Heliotropium crispum Desf., a relatively under-explored medicinal plant species. Methanolic extracts prepared from a whole plant of H. crispum were studied for phytochemical composition and possible in vitro and in silico biological properties. Antioxidant potential was assessed via six different assays, and enzyme inhibition potential against key clinical enzymes involved in neurodegenerative diseases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), diabetes (α-amylase and α-glucosidase), and skin problems (tyrosinase) was assayed. Phytochemical composition was established via determination of the total bioactive contents and reverse phase ultra-high performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Chemical profiling revealed the tentative presence of 50 secondary metabolites. The plant extract exhibited significant inhibition against AChE and BChE enzymes, with values of 3.80 and 3.44 mg GALAE/g extract, respectively. Further, the extract displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 43.19 and 41.80 mg TE/g extract, respectively. In addition, the selected compounds were then docked against the tested enzymes, which have shown high inhibition affinity. To conclude, H. crispum was found to harbor bioactive compounds and showed potent biological activities which could be further explored for potential uses in nutraceutical and pharmaceutical industries, particularly as a neuroprotective agent.
Antifreeze proteins (AFPs) are specific proteins, glycopeptides, and peptides made by different organisms to allow cells to survive in sub-zero conditions. AFPs function by reducing the water's freezing point and avoiding ice crystals' growth in the frozen stage. Their capability in modifying ice growth leads to the stabilization of ice crystals within a given temperature range and the inhibition of ice recrystallization that decreases the drip loss during thawing. This review presents the potential applications of AFPs from different sources and types. AFPs can be found in diverse sources such as fish, yeast, plants, bacteria, and insects. Various sources reveal different α-helices and β-sheets structures. Recently, analysis of AFPs has been conducted through bioinformatics tools to analyze their functions within proper time. AFPs can be used widely in various aspects of application and have significant industrial functions, encompassing the enhancement of foods' freezing and liquefying properties, protection of frost plants, enhancement of ice cream's texture, cryosurgery, and cryopreservation of cells and tissues. In conclusion, these applications and physical properties of AFPs can be further explored to meet other industrial players. Designing the peptide-based AFP can also be done to subsequently improve its function.
The Krüppel-like factors (KLFs) family of proteins control several key biological processes that include proliferation, differentiation, metabolism, apoptosis and inflammation. Dysregulation of KLF functions have been shown to disrupt cellular homeostasis and contribute to disease development. KLF6 is a relevant example; a range of functional and expression assays suggested that the dysregulation of KLF6 contributes to the onset of cancer, inflammation-associated diseases as well as cardiovascular diseases. KLF6 expression is either suppressed or elevated depending on the disease, and this is largely due to alternative splicing events producing KLF6 isoforms with specialised functions. Hence, the aim of this review is to discuss the known aspects of KLF6 biology that covers the gene and protein architecture, gene regulation, post-translational modifications and functions of KLF6 in health and diseases. We put special emphasis on the equivocal roles of its full-length and spliced variants. We also deliberate on the therapeutic strategies of KLF6 and its associated signalling pathways. Finally, we provide compelling basic and clinical questions to enhance the knowledge and research on elucidating the roles of KLF6 in physiological and pathophysiological processes.
Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.