Emotional Stress and Immune Response in Surgery: A Psychoneuroimmunological Perspective.

Psychoneuroimmunology (PNI) offers a deep dive into the nexus between emotional stress, immunity, and surgical outcomes. In this narrative review, we first trace PNI's historical roots, providing a foundational understanding of its evolution. We then dissect its significance across the surgical journey, from the preoperative phase through to postoperative recovery. It becomes evident through our exploration that emotional stress has profound implications for surgery, notably influencing wound healing rates, susceptibility to infections, and overall postoperative well-being. Among the arsenal to combat these challenges, interventions such as cognitive-behavioral therapy, mindfulness, and complementary practices such as meditation and yoga have emerged as potent tools. They not only mitigate stress but also play a pivotal role in enhancing immune function. However, the journey to optimizing surgical outcomes is not just about identifying effective interventions. A resounding theme is the importance of holistic care, ensuring that all patients have equitable access to these tools. As PNI continues to evolve, we stand at the precipice of a healthcare revolution, one that promises a blend of personalized care, anchored in a deep understanding of the mind-body connection in surgical contexts.

Harmonizing Medicine and Surgery in the Pursuit of Boolean Remission: A Rheumatological Magnum Opus.

Rheumatic diseases encompass a diverse group of musculoskeletal conditions that often lead to inflammation, pain, and significant limitations in patients' lives. While traditional treatment approaches have primarily centered on medications to control symptoms, recent developments have introduced the concept of Boolean remission. Boolean remission offers a comprehensive evaluation of disease activity by considering clinical, biochemical, and patient-reported outcomes. This narrative review explores the multifaceted landscape of Boolean remission in the context of rheumatic diseases, with a focus on rheumatoid arthritis (RA), as it remains a substantial clinical challenge. The review outlines the definition, criteria, historical context, and development of Boolean remission, shedding light on its emergence as a more patient-centered and stringent treatment goal. The role of pharmacological interventions, including immunomodulators and biologics, in achieving Boolean remission is discussed, emphasizing the significance of treatment protocols that encompass regular monitoring, medication adjustment, shared decision-making, and patient education. Surgical interventions, such as joint replacements and synovectomies, complement medication-based strategies when joint damage becomes severe, with adherence to surgical protocols ensuring sustained Boolean remission. The integration of medicine and surgery through integrated care models and interdisciplinary teams is examined as a critical aspect of optimizing patient outcomes. Boolean remission's broader impact on healthcare policies and clinical trial endpoints is explored, underscoring its growing significance in rheumatic disease management. The review concludes by looking toward the future, where emerging technologies, biomarkers, and personalized medicine approaches hold promise in refining Boolean remission criteria and making it a more attainable and impactful treatment goal. Policy implications suggest the integration of Boolean remission into healthcare quality metrics, incentivizing healthcare providers to prioritize this rigorous standard of care. Boolean remission represents a pivotal shift in the holistic and patient-centered management of rheumatic diseases, offering hope for improved patient outcomes and enhanced quality of life in this challenging clinical landscape.

Exploring therapeutic targets and drug candidates for obesity: a combined network pharmacology, bioinformatics approach.

The remarkably high prevalence of obesity in Saudi Arabia reflects a global epidemic demanding urgent attention due to its associated health risks. The integration of traditional medicine, a vital cultural aspect, involves the use of medicinal plants to address various diseases, including obesity. This research merges network pharmacology (NP) and bioinformatics to innovate obesity treatment by identifying effective phytochemicals from native plants in the Taif valley. Focusing on six indigenous plants-Senna alexandrina, Capsicum annuum, Zingiber officinale, Curcuma longa, Trigonella foenum-graecum, and Foeniculum vulgare-we conducted preliminary screenings for potential bioactive compounds. We systematically compiled compound data from public databases and reviewed literature, revealing active compounds like apigenin, kaempferol, moupinamide, cyclocurcumin, chrysoeriol, isorhamnetin, rheinanthrone, cyclocurcumin, and riboflavin.Constructing a compound-target genes-obesity network unveiled their significant impact on metabolic regulation and fat accumulation, interacting notably with key proteins AKT1 and PTGS2. Molecular docking and 100 ns Molecular Dynamic (MD) simulations demonstrated robust binding affinity and stability at the docking site. Employing adipocytes as a cellular model, we gauged their viability and response to obesity-related stressors post-treatment with these native plant compounds.In conclusion, Saudi Arabia's indigenous plants hold promise as natural solutions for obesity treatment. This research opens new avenues in the battle against this pervasive health crisis by incorporating the potential of native botanicals.Communicated by Ramaswamy H. Sarma.

Beneath the Layers: Deciphering the Molecular Pathways, Therapeutic Avenues, and Neurological Connections of Soft Tissue Sarcomas.

Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that have long posed challenges in terms of diagnosis, treatment, and management. This narrative review provides a comprehensive exploration into the multifaceted realm of STS, spanning from its historical origins to the latest advancements in research and clinical care. We delve into the molecular intricacies of STS, highlighting the genetic and epigenetic aberrations that drive these tumors. The review emphasizes the neurological implications of STS, a relatively underexplored area, shedding light on the interplay between tumor biology and neural processes. The evolving therapeutic landscape is discussed, with a focus on the promise of targeted therapies, immunotherapy, and precision medicine. A significant portion is dedicated to the patient-centric approach, underscoring the importance of holistic care that addresses both the physical and psychological needs of STS patients. Furthermore, we highlight the gaps in current research and clinical practices, offering insights into potential avenues for future exploration. This review serves as a valuable resource for clinicians, researchers, and the broader scientific community, encapsulating the current state of STS knowledge and pointing toward future directions in this dynamic field.

Clinostomum complanatum: Anthelmintic potential of curcumin on the infective progenetic metacercarial stage.

The emerging resistance against commonly used antiparasitic drugs has driven investigators to explore alternative approaches using plant-derived active ingredients. These compounds have been tested for antiviral, antibacterial, and anthelmintic properties, particularly against adult worms. However, their effects on larval forms have been neglected. Curcumin is a polyphenol that is a significant constituent of the rhizome of Curcuma longa and possesses various biological activities, including antioxidant, anti-inflammatory, anti-infectious, and anti-carcinogenic. In the present study, the anthelmintic potential of curcumin was tested in vitro for its efficacy against the zoonotically important larval form, the progenetic metacercariae of Clinostomum complanatum, which were procured from the forage fish, Trichogaster fasciatus. Curcumin produced time and concentration-dependent inhibition in the motility of treated metacercarial worms, with the maximum inhibition of motility reported at 60 µM along with a significant increase of (36-92%) in ROS and (57-112%) in GSH levels at the end of a period of 6 h. In contrast, curcumin at the highest concentration significantly inhibited the activities of the antioxidant and detoxification enzymes SOD (36%) and GST (16%), respectively, in addition to altering the polypeptide profile and inhibiting cysteine proteases. The tegumental surface appeared to be highly disrupted in curcumin-treated worms, exhibiting severe blebbing, shearing of the tegument, and spine erosion. Such changes would affect the tegumental functions and survival of worms in the hostile microenvironment. This would render worms more susceptible to host-mediated rejection responses. Based on the results of the present study, it is inferred that C. complanatum could serve as an excellent model for screening novel anthelmintic drugs against larval trematodes of great economic significance. Furthermore, we conclude that curcumin could be exploited as an excellent phytotherapeutic agent against the virulent larval form under investigation.

Application of essential oils as natural biopesticides; recent advances.

There is an urgent need for the development of sustainable and eco-friendly pesticide formulations since common synthetic pesticides result in many adverse effects on human health and the environment. Essential oils (EOs) are a mixture of volatile oils produced as a secondary metabolite in medicinal plants, and show activities against pests, insects, and pathogenic fungi. Their chemical composition is affected by several factors such as plant species or cultivar, geographical origin, environmental conditions, agricultural practices, and extraction method. The growing number of studies related to the herbicidal, insecticidal, acaricidal, nematicidal, and antimicrobial effects of EOs demonstrate their effectiveness and suitability as sustainable and environment-friendly biopesticides. EOs can biodegrade into nontoxic compounds; at the same time, their harmful and detrimental effects on non-target organisms are low. However, few biopesticide formulations based on EOs have been turned into commercial practice upto day. Several challenges including the reduced stability and efficiency of EOs under environmental conditions need to be addressed before EOs are widely applied as commercial biopesticides. This work is an overview of the current research on the application of EOs as biopesticides. Findings of recent studies focusing on the challenges related to the use of EOs as biopesticides are also discussed.

Cottonseed oil: A review of extraction techniques, physicochemical, functional, and nutritional properties.

Seed oils are the richest source of vitamin-E-active compounds, which contribute significantly to antioxidant activities. Cottonseed oil (CS-O) is attaining more consideration owing to its high fiber content and stability against auto-oxidation. CS-O has gained a good reputation in the global edible oil market due to its distinctive fatty acid profile, anti-inflammatory, and cardio-protective properties. CS-O can be extracted from cottonseed (CS) by microwave-assisted extraction (MAE), aqueous/solvent extraction (A/SE), aqueous ethanol extraction (A-EE), subcritical water extraction, supercritical carbon dioxide extraction (SC-CO2), and enzyme-assisted extraction (E-AE). In this review, the importance, byproducts, physicochemical characteristics, and nutritional profile of CS-O have been explained in detail. This paper also provides a summary of scientific studies existing on functional and phytochemical characteristics of CS-O. Its consumption and health benefits are also deliberated to discover its profitability and applications. CS-O contains 26-35% saturated, 42-52% polyunsaturated, and 18-24% monounsaturated FA. There is approximately 1000 ppm of tocopherols in unprocessed CS-O, but up to one-third is lost during processing. Moreover, besides being consumed as cooking oil, CS-O discovers applications in many fields such as biofuel, livestock, cosmetics, agriculture, and chemicals. This paper provides a comprehensive review of CS-O, its positive benefits, fatty acid profile, extraction techniques, and health applications.HighlightsCS-O is a rich source of exceptional fatty acids.Various techniques to extract the CS-O are discussed.Numerous physicochemical properties of CS-O for the potential market are assessed.It has a wide range of functional properties.Nutritional quality and health benefits are also evaluated.

Short-term responses of Spinach (Spinacia oleracea L.) to the individual and combinatorial effects of Nitrogen, Phosphorus and Potassium and silicon in the soil contaminated by boron.

While of lesser prevalence than boron (B) deficient soils, B-rich soils are important to study as they can cause B toxicity in the field and subsequently decrease crop yields in different regions of the world. We have conducted the present study to examine the role of the individual or combined application of silicon (Si) and NPK fertilizer in B-stressed spinach plants (Spinacia oleracea L.). S. oleracea seedlings were subjected to different NPK fertilizers, namely, low NPK (30 kg ha-2) and normal NPK (60 kg ha-2)], which were also supplemented by Si (3 mmol L-1), for varying levels of B in the soil i.e., 0, 250, and 500 mg kg-1. Our results illustrated that the increasing levels of B in the soil caused a substantial decrease in the plant height, number of leaves, number of stems, leaf area, plant fresh weight, plant dry weight, chlorophyll a, chlorophyll b, total chlorophyll, carotenoid content, net photosynthesis, stomatal conductance, transpiration rate, magnesium content in the roots, magnesium contents in the shoots, phosphorus content in the roots, phosphorus content in the leaves in the shoots, iron content in the roots, iron content in the shoots, calcium content in the roots, and calcium content in the shoots. However, B toxicity in the soil increased the concentration of malondialdehyde, hydrogen peroxide, and electrolyte leakage which were also manifested by the increasing activities of enzymatic [superoxidase dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)], and non-enzymatic antioxidants (phenolic, flavonoid, ascorbic acid, and anthocyanin content). B toxicity in the soil further increased the concentration of organic acids in the roots such as oxalic acid, malic acid, formic acid, citric acid, acetic acid, and fumaric acid. The addition of Si and fertilizer levels in the soil significantly alleviated B toxicity effects on S. oleracea by improving photosynthetic capacity and ultimately plant growth. The increased activity of antioxidant enzymes in Si and NPK-treated plants seems to play a role in capturing stress-induced reactive oxygen species, as was evident from the lower levels of oxidative stress indicators, organic acid exudation, and B concentration in the roots and shoots of Si and NPK-treated plants. Research findings, therefore, suggested that the Si and NPK application can ameliorate B toxicity in S. oleracea seedlings and result in improved plant growth and composition under metal stress as depicted by the balanced exudation of organic acids.

Influence of diverse natural biopolymers on the physicochemical characteristics of borage seed oil-peppermint oil loaded W/O/W nanoemulsions entrapped with lycopene.

Borage seed oil (BSO), peppermint oil (PO) and lycopene (LC) have accomplished a lot of interest due to their therapeutic benefits in the food and pharmaceutical sectors. However, their employment in functional food products and dietary supplements is still precluded by their high susceptibility to oxidation. Thus, the encapsulation can be applied as a promising strategy to overcome these limits. In the present study, doubly layered water/oil/water (W/O/W) nanoemulsions were equipped using purity gum ultra (PGU), soy protein isolate (SPI), pectin (PC), whey protein isolate (WPI) and WPI-PC and SPI-PC complexes, and their physico-chemical properties were investigated. Our aim was to investigate the influence of natural biopolymers as stabilizers on the physicochemical properties of nanoemulsified BSO, PO and lycopene thru W/O/W emulsions. The droplet size of the fabricated emulsions coated with PGU, WPI, SPI, PC, WPI-PC, and SPI-PC was 156.2, 265.9, 254.7, 168.5, 559.5 and 656.1 nm, correspondingly. The encapsulation efficiency of the entrapped bioactives for powders embedded by PGU, WPI, SPI, PC, WPI-PC, and SPI-PC was 95.21%, 94.67%, 97.24%, 92.19%, 90.07% and 92.34%, respectively. In addition, peroxide and p-anisidine values were used to measure the antioxidant potential of the entrapped bioactive compounds during storage, which was compared to synthetic antioxidant and bare natural antioxidant. The collected findings revealed that oxidation occurred in oils encompassing entrapped bioactive compounds, but at a lower extent than for non-encapsulated bioactives. In summary, the findings obtained from current research prove that the nanoencapsulation of BSO surrounded by innermost aqueous stage of W/O/W improved its stability as well as allowed a controlled release of the entrapped bioactives. Thus, the obtained BSO-PO-based systems could be successfully used for further fortification of food-stuffs.

Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis.

Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins-calcium binding and mycosubtilin synthase subunit C-as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.

Spray dried nanoemulsions loaded with curcumin, resveratrol, and borage seed oil: The role of two different modified starches as encapsulating materials.

Recently, food industries are directing on the promotion of innovative food matrices fortified with bioactive compounds in order to enhance the consumer's health. Octenyl succinic anhydride modified starches (OSA-MS) such as Hi-cap100 (HCP) and purity gum 2000 (PUG) were used to fabricate emulsions co-entrapped with borage seed oil (BSO), resveratrol (RES) and curcumin (CUR), which were further spray dried to obtain powders. The fabricated microcapsules loaded with BSO, RES, and CUR displayed excellent dissolution performance, high encapsulation efficiency (≈93.05%) as well as semi-spherical shape, revealed via scanning electron microscopy (SEM). We also evaluated the impact of storage time (4 weeks) and temperature (40 °C) on the physicochemical characterization of OSA-MS coated microcapsules. Microcapsules coated with HCP exhibited greater oxidative stability, lower water activity and moisture contents rather than PUG coated microcapsules during storage because of its good film-forming properties. Addition of CUR enhanced the oxidative stability and retention of bioactive compounds. HCP microcapsules loaded with BSO + RES + CUR presented supreme retention of RES (70.32%), CUR 81.6% and γ-linolenic acid (≈ 96%). Our findings showed that CUR acted as an antioxidant agent; also, lower molecular weight OSA-MS as wall material could be used for the entrapment of bioactive compounds and promotion of innovative food products.

In vitro and in silico Xanthine Oxidase Inhibitory Activity of Selected Phytochemicals Widely Present in Various Edible Plants.

AIM AND OBJECTIVE: The present study was designed to evaluate the xanthine oxidase (XO) inhibitory and antioxidant activities of 30 bioactive compounds present in edible food plants for the possible treatment of hyperuricemia. MATERIALS AND METHODS: The XO inhibitory, SO and DPPH radical scavenging activities of selected dietary polyphenols were determined by using colorimetric assays. The molecular docking analysis was performed to evaluate the insight into inhibitory mode of action of bioactive compounds against XO. RESULTS: The results show that apigenin, galangin, kaempferol, quercetin, genistein and resveratrol potently inhibit XO enzyme among all tested compounds. Flavonoids exhibit higher, anthocyanins and hydroxycinnamic acids moderate, maslinic acid, ellagic acid, salicylic acid, [6]-gingerol and flavan-3-ols showed weak XO inhibitory activity. The results of molecular docking study revealed that these bioactive compounds bind with the active site of XO and occupy the active site which further prevents the entrance of substrate and results in the inhibition of XO. CONCLUSION: Inhibition of XO gives a robust biochemical basis for management of hyperuricemia, gout and other associated diseases via controlling uric acid synthesis.

Role of peppermint oil in improving the oxidative stability and antioxidant capacity of borage seed oil-loaded nanoemulsions fabricated by modified starch.

Borage seed oil (BSO) is one of the richest sources of γ-linolenic acid and linoleic acid, which are considered to retain plenty of health promoting benefits. However, its application in functional foods and dietary supplements remains limited owing to its superior vulnerability to oxidation. To solve this problem, ultrasound-assisted BSO-loaded nanoemulsions were prepared with modified starch incorporating different concentrations of peppermint oil (PO), as a natural antioxidant. The influence of different PO levels on the mean droplet size, rheology attributes, and oxidative stability of nanoemulsions stored at various temperatures (4, 25, and 40 °C) during 30 days storage was analyzed. In addition, DPPH and ABTS assays were used to determine the antioxidant activity and antioxidant capacity of BSO-loaded nanoemulsions, respectively. The optimized formulation (NE3; 5:5% v/v PO: BSO) exhibited a slight change in droplet size and oxidative stability at all temperatures during storage compared to other formulations. At a concentration of 328.08 µL/mL, formulation NE3 presented the minimum DPPH IC50 at 40 °C, which was lower than other formulations. The findings of this study revealed that the maximum retained antioxidant capacity (99.42 µg Trolox/mL) was related to NE3 comprising (5:5% v/v PO: BSO) stored at 40 °C for 30 days; which could be accredited to the role of PO as a natural antioxidant in order to improve the oxidative stability of nanoemulsion delivery system. Taken together, co-encapsulation of BSO and PO within nanoemulsions provides novel insights regarding the development of functional foods, dietary supplements and beverages.

Generation of oxidative stress and induction of apoptotic like events in curcumin and thymoquinone treated adult Fasciola gigantica worms.

Fasciolosis is a neglected tropical disease caused by the liver fluke Fasciola gigantica. The absence of successful vaccine and emerging resistance in flukes against the drug of choice, triclabendazole, has necessitated the search for alternatives including phyto-therapeutic approaches. Curcumin and thymoquinone, the active ingredients of Curcuma longa and Nigella sativa plants respectively, were first screened for their binding affinity with Glutathione-S-transferase (GST) molecule through in silico molecular docking followed by in vitro treatment of worms with varying concentrations of the test compounds. The in silico molecular docking of curcumin and thymoquinone with sigma GST revealed strong hydrogen bonding as well as hydrophobic interactions with high fitness scores but showing inter-specific differences. The in vitro treatment of F. gigantica worms with both curcumin and thymoquinone resulted in a significant increase in the generation of reactive oxygen species (ROS) whereas the level of reduced glutathione, a primary redox regulator, was found to be significantly decreased (p < 0.05). The two compounds not only inhibited the GST activity, which is an important detoxification enzyme and also a key drug/vaccine target for the control of fasciolosis but also significantly inhibited the activity of antioxidant enzymes glutathione peroxidase and glutathione reductase that are vital in maintenance of redox homeostasis. The immunohistochemistry performed using anti sigma GST polyclonal antibodies revealed that both the compounds used in the present study significantly reduced immunofluorescence in the vitellaria, developing eggs present in the ovary and the intestinal caecae indicating inhibition of GST enzyme in these regions of the worms. Further, following treatment with curcumin and thymoquinone, chromatin condensation and DNA fragmentation was also observed in F. gigantica worms. In conclusion, both curcumin and thymoquinone generated oxidative stress in the worms by production of ROS and significantly inhibiting their antioxidant and detoxification ability. The oxidative stress along with induction of apoptotic like events would compromise the survival ability of worms within the host. However, further studies are required to establish their anthelmintic potential alone and in combination with the commonly used anthelmintic drugs under in vivo conditions.

Interleukin-1beta induces CREB-binding protein (CBP) mRNA in brain and the sequencing of rat CBP.

Interleukin-1 beta (IL-1) and CREB have many CNS actions including sleep regulation and hippocampal-dependent learning. CREB acts in part via CREB-binding protein (CBP). We thus determined whether IL-1 could induce CBP gene expression. Initially, cultured hippocampal cells were treated with IL-1 and differential display reverse transcription was used to identify up- and down-regulated genes. We then sequenced rat CBP. Of the IL-1-upregulated genes, CBP and adenine nucleotide translocator-1 (ANT-1) were investigated in vivo. In these experiments, IL-1 was given to rats intraventricularly and sacrificed 2 h later; both CBP and ANT-1 transcripts were upregulated in the cerebral cortex and hypothalamus. We conclude that rat CBP shares many of the functional domains as human and murine CBP and that IL-1 upregulates genes previously associated with learning and sleep.