The impact of different levels of wheat diets on hepatic oxidative stress, immune response, and lipid metabolism in Tibetan sheep (Ovis aries).

BACKGROUND: Compared with corn, wheat contains higher crude protein, amino acids concentration. However, wheat contains a mass of anti-nutritional factors, resulting in increased of the digesta viscosity and impaired the intestinal function in ruminant. OBJECTIVE: This study aimed to investigate the effects of substitution of different amounts of wheat for corn on hepatic metabolism in the Tibetan lamb. METHODS: Ninety Tibetan lambs (Body weight = 12.37 ± 0.92 kg) were randomly assigned to three groups: 0% wheat diet (Control), 10% wheat diet (Low group), and 15% wheat diet (High group). The feeding trial lasted for 130 d, including a 10 d adaption period. Hepatic gene expression profiling was performed via RNA sequencing after the conclusion of the feeding trials. RESULTS: Results showed that greater level of glutathione peroxidase levels in L group compared with those of the C and H groups (P < 0.05). The immune indexes, including interleukin-1ß (IL-1ß), immunoglobulin A (IgA), and IgM were also elevated in L group compared with the other groups (P < 0.05). Compared with H group, the hepatocytes were arranged radially, and hepatic plates anastomosed with each other to form a labyrinth-like structure in L group. Transcriptomic analysis showed 872 differentially expressed genes (DEG) between H and L group, of which 755 were down-regulated and 117 were up-regulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 32 pathways were significantly enriched (Q-value < 0.05), such as the cAMP signaling pathway, Th1 and Th2 cell differentiation, leukocyte transendothelial migration, platelet activation and adipocytokine signaling pathway. Additionally, the expression of comment DEGs were verified via quantitative reverse-transcription polymerase chain reaction. CONCLUSION: In summary, our findings suggest that wheat can be supplemented up to 10% in Tibetan sheep, contributing to improve the hepatic oxidative stress, immune response and lipid metabolism through regulating the expression of related genes.

Molecular dynamics exploration of Lupenone: therapeutic implications for glioblastoma multiforme and alzheimer's amyloid beta pathogenesis.

Neuro-oncological and neurodegenerative disorders, represented paradigmatically by glioblastoma and Alzheimer's disease, respectively, persist as formidable challenges in the biomedical realm. The interconnected molecular underpinnings of these conditions necessitate rigorous and novel therapeutic examinations. This comprehensive research was anchored on the premise of unveiling the therapeutic potential and specificity of Lupenone, a potent phytoconstituent, in targeting the molecular pathways underpinning both glioblastoma and Alzheimer's amyloid beta pathology. This was gauged through its interactions with key protein structures, 5H08 and 2ZHV. An integrative approach was adopted, marrying advanced proteomics and modern computer-aided drug design techniques. Molecular docking of Lupenone with 5H08 and 2ZHV was meticulously executed, with subsequent molecular dynamics simulations providing insights into the stability, viability, and intricacies of these interactions. Lupenone demonstrated profound binding affinities, evidenced by robust docking scores of -9.54 kcal/mol for 5H08 and -10.59 kcal/mol for 2ZHV. These interactions underscored Lupenone's eminent therapeutic potential in mitigating glioblastoma and modulating the amyloid beta pathology inherent to Alzheimer's. The introduction of Proteolysis Targeting Chimeras (PROTACs) further magnified the therapeutic prospects, accentuating Lupenone's efficacy. The findings of this study not only underscore the therapeutic acumen of Lupenone in addressing the challenges posed by glioblastoma and Alzheimer's but also lay a strong foundation for its consideration as a leading candidate in future neuro-oncological and neurodegenerative research endeavors. Given the compelling in-silico data, a clarion call is made for its empirical validation in holistic in-vivo settings, potentially pioneering a new therapeutic epoch in both glioblastoma and Alzheimer's interventions.

Antifungal and Antiproliferative Activity of Pistagremic Acid and Flavonoids Extracted from the Galls of Pistacia chinensis subsp. integerrima.

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.

Green synthesis of silver and gold nanoparticles in Callistemon viminalis extracts and their antimicrobial activities.

In the current study, the bottlebrush [Callistemon viminalis (Sol. ex Gaertn.) G. Don] plant was selected for the green synthesis of silver (Ag) and gold (Au) nanoparticles and to evaluate its antibacterial and antifungal activities. Phytochemical screening of C. viminalis confirmed the presence of alkaloids, anthraquinones, saponins, tannins, betacyanins, phlobatanins, coumarins, terpenoids, steroids, glycosides, and proteins. To characterize the synthesized Ag and Au NPs, UV-Visible spectroscopy, FTIR spectroscopy for functional group identification, field emission scanning electron microscopy (FE-SEM) for particle size, and elemental analysis were performed using EDX. The UV-Visible absorption spectra of the green-synthesized Ag and Au nanoparticles were found to have a maximum absorption band at 420 nm for Ag NPs and 525 nm for Au NPs. FE-SEM analysis of the synthesized NPs revealed a circular shape with a size of 100 nm. Elemental analysis was performed for the synthesis of Ag and Au NPs, which confirmed the purity of the nanoparticles. The greenly synthesized Ag and Au NPs were also evaluated for their anti-bacterial and anti-fungal activities, which exhibited prominent inhibition activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans, C. krusei, Aspergillus sp., and Trichoderma species. The highest zone of inhibition 15.5 ± 0.75 and 15 ± 0.85 mm was observed for Ag NPs against E. coli and P. aeruginosa. Similarly, Trichoderma sp. and Aspergillus sp. were inhibited by Ag NPs up to 13.5 ± 0.95 and 13 ± 0.70 mm. This work will open doors for the development of new antimicrobial agents using green chemistry.

Fat deposition, fatty acid profiles, antioxidant capacity and differentially expressed genes in subcutaneous fat of Tibetan sheep fed wheat-based diets with and without xylanase supplementation.

Xylanase, an exogenous enzyme that plays an essential role in energy metabolism by hydrolysing xylan into xylose, has been shown to positively influence nutrient digestion and utilisation in ruminants. The objective of this study was to evaluate the effects of xylanase supplementation on the back-fat thickness, fatty acid profiles, antioxidant capacity, and differentially expressed genes (DEGs) in the subcutaneous fat of Tibetan sheep. Sixty three-month-old rams with an average weight of 19.35 ± 2.18 kg were randomly assigned to control (no enzyme added, WH group) and xylanase (0.2% of diet on a dry matter basis, WE group) treatments. The experiment was conducted over 97 d, including 7 d of adaption to the diets. The results showed that xylanase supplementation in the diet increased adipocyte volume of subcutaneous fat (p < 0.05), shown by hematoxylin and eosin (H&E) staining. Gas chromatography showed greater concentrations of C14:0 and C16:0 in the subcutaneous fat of controls compared with the enzyme-treated group (p < 0.05), while opposite trend was seen for the absolute contents of C18:1n9t, C20:1, C18:2n6c, C18:3, and C18:3n3 (p < 0.05). Compared with controls, supplementation with xylanase increased the activity of T-AOC significantly (p < 0.05). Transcriptomic analysis showed the presence of 1630 DEGs between the two groups, of which 1023 were up-regulated and 607 were down-regulated, with enrichment in 4833 Gene Ontology terms, and significant enrichment in 31 terms (p < 0.05). The common DEGs were enriched in 295 pathways and significantly enriched in 26 pathways. Additionally, the expression of lipid-related genes, including fatty acid synthase, superoxide dismutase, fatty acid binding protein 5, carnitine palmytoyltransferase 1 A, and peroxisome proliferator-activated receptor A were verified via quantitative reverse-transcription polymerase chain reaction. In conclusion, dietary xylanase supplementation was found to reduce subcutaneous fat deposition in Tibetan sheep, likely through modulating the expression of lipid-related genes.

Natural plant products as effective alternatives to synthetic chemicals for postharvest fruit storage management.

Fruits contain enormous source of vitamins that provides energy to the human body. These are also affluent in essential and vital vitamins, minerals, fiber, and health-promoting components, which has led to an increase in fruit consumption in recent years. Though fruit consumption has expanded considerably in recent years, the use of synthetic chemicals to ripen or store fruits has been steadily increasing, resulting in postharvest deterioration. Alternatives to synthetic chemicals should be considered to control this problem. Instead of utilizing synthetic chemicals, this study suggests using natural plant products to control postharvest decay. The aim of this study indicates how natural plant products can be useful and effective to eliminate postharvest diseases rather than using synthetic chemicals. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE, and CNKI Scholar. The current review focused on the postharvest of fruits has become more and more necessary because of these vast demands of fruits. Pathogen-induced diseases are the main component and so the vast portion of fruits get wasted after harvest. Besides, it may occur harmful during harvesting and subsequent handling, storage, and marketing and after consumer purchasing and also causes for numerous endogenous and exogenous diseases via activating ROS, oxidative stress, lipid peroxidation, etc. However, pathogenicity can be halted by using postharvest originating natural fruits containing bioactive elements that may be responsible for the management of nutritional deficiency, inflammation, cancer, and so on. However, issues arising during the postharvest diseases must be controlled and resolved before releasing the horticultural commodities for commercialization. Therefore, the control of postharvest pathogens still depends on the use of synthetic fungicides; however, due to the problem of the development of the fungicide-resistant strains there is a good demand of public to eradicate the use of pesticides with the arrival of numerous diseases that are expanded in their intensity by the specific chemical product. By using of the organic or natural products for controlling postharvest diseases of fruits has become a mandatory step to take. In addition, antimicrobial packaging may have a greater impact on long-term food security by lowering the risk of pathogenicity and increasing the longevity of fruit shelf life. Taken together, natural chemicals as acetaldehyde, hexanal, eugenol, linalool, jasmonates, glucosinolates, essential oils, and many plant bioactive are reported for combating of the postharvest illnesses and guide to way of storage of fruits in this review.

Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update.

Olive family (Oleaceae) contains several species among which Olea europaea L. is mostly used for production of olive oils. Various parts of olive tree are rich source of diverse bioactive compounds such as Apigenin, elenolic acid, Hydroxytyrosol, Ligstroside, Oleoside, Oleuropein, Oleuropein aglycone, Tyrosol, etc. Among these, oleuropein, a secoiridoid is predominantly found in olive leaves and young olive fruits of different species of Oleaceae family. Scientists have adopted numerous extraction methods (conventional & latest) to increase the yield of oleuropein. Among these techniques, maceration, soxhlet, microwave-assisted, ultrasonication, and supercritical fluid methods are most commonly employed for extraction of oleuropein. Evidently, this review emphasizes on various in-vitro and in-vivo studies focusing on nutraceutical properties of oleuropein. Available literature highlights the pharmaceutical potential of oleuropein against various diseases such as obesity, diabetes, cardiovascular complications, neurodegenerative diseases, cancer, inflammation, microbial infections, and oxidation. This review will benefit the scientific community as it narrates comprehensive literature regarding absorption, metabolism, bioavailability, extraction techniques, and nutraceutical perspectives associated with oleuropein.

Salvia officinalis L. Methanolic Extract Reduces Lead and Nicotine-Induced Sperm Quality Degeneration in Male Rats.

Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220-250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats' fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.

Assessment of Bioactive Phytochemicals and Utilization of Rosa canina Fruit Extract as a Novel Natural Antioxidant for Mayonnaise.

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g-1), total flavonoids content (26.31 ± 1.03 mg QE g-1), and free radical scavenging activity. The GC-MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods.

A renewed concept on the MAPK signaling pathway in cancers: Polyphenols as a choice of therapeutics.

Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer.

Nutritional and health beneficial properties of saffron (Crocus sativus L): a comprehensive review.

Saffron (Crocus sativus L., family Iridaceae) is used traditionally for medicinal purpose in Chinese, Ayurvedic, Persian and Unani medicines. The bioactive constituents such as apocarotenoids, monoterpenoids, flavonoids, phenolic acids and phytosterols are widely investigated in experimental and clinical studies for a wide range of therapeutic effects, especially on the nervous system. Some of the active constituents of saffron have high bioavailability and bioaccessibility and ability to pass the blood-brain barrier. Multiple preclinical and clinical studies have supported neuroprotective, anxiolytic, antidepressant, learning and memory-enhancing effect of saffron and its bioactive constituents (safranal, crocin, and picrocrocin). Thus, this plant and its active compounds could be a beneficial medicinal food ingredient in the formation of drugs targeting nervous system disorders. This review focuses on phytochemistry, bioaccessibility, bioavailability, and bioactivity of phytochemicals in saffron. Furthermore, the therapeutic effect of saffron against different nervous system disorders has also been discussed in detail.

In Vivo and In Vitro Biological Evaluation and Molecular Docking Studies of Compounds Isolated from Micromeria biflora (Buch. Ham. ex D.Don) Benth.

Micromeria biflora, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of Micromeria biflora led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety.

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer.

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulating cell signaling pathways. Resveratrol is a well-known polyphenolic molecule with antioxidant, anti-inflammatory, and health-prompting effects among which its anticancer role has been best defined. Additionally, this polyphenol has confirmed its role in cancer management because it activates tumor suppressor genes, suppresses cell proliferation, induces apoptosis, inhibits angiogenesis, and modulates several other cell signaling molecules. The anticancer potential of resveratrol is recognized in numerous in vivo and in vitro studies. Previous experimental data suggested that resveratrol may be valuable in cancer management or improve the efficacy of drugs when given with anticancer drugs. This review emphasizes the potential role of resveratrol as an anticancer drug by modulating numerous cells signaling pathways in different types of cancer.

Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects.

INTRODUCTION: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. OBJECTIVE: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. MATERIALS AND METHODS: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. RESULTS: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. CONCLUSIONS: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Absence of CD74 Isoform at 41kDa Prevents the Heterotypic Associations between CD74 and CD44 in Human Lung Adenocarcinoma-derived Cells.

Lung cancer is a leading cause of cancer-associated death in all over the globe. This study was undertaken to determine the expression and interaction of membrane-bound receptors CD74 and CD44 in human lung adenocarcinoma cells and their associated signaling was also attempted. Levels of CD74 and CD44 were studied in human lung adenocarcinoma-evolved cells A549 and H460. CD74-mediated downstream signaling was studied by the nuclear-transcription-factor NF-κB and prostaglandin E2 (PGE2) production. Flow-cytometric analysis showed that both CD74 and CD44 were perfectly expressed in A549 cells. Importantly, Western immunoblotting showed that A549 cells expressed only two isoforms of CD74 at 33 and 35 kDa but isoform at 41 kDa was absent. These results were verified in H460 cells. Confocal microscopy showed CD74 and CD44 was colocalized but heterotypic interaction between them was missing in both A549 and H460 cells. Activation of NF-κB and production of PGE2 in human lung cancer cells were comparable with other cancer cells. In conclusion, this is the first study that shows A549 and H460 cells expressed two distinctive isoforms of CD74 but isoform at 41 kDa was absent. Due to the absence of this isoform, the direct physical interaction between them CD74 and CD44 was lacking. Furthermore, the data also demonstrated that lacking of direct physical interaction between CD74 and CD44 had no effect on NF-κB activation and PGE2 production indicating that CD74-mediated downstream signaling occurs either through coreceptors or indirect interaction with CD44 in human lung cancer cells.Abbreviation: CD: cluster of differentiation; SCLC: small cell lung cancer; NSCLC: nonsmall cell lung cancer; SCC: squamous cell carcinoma; ADC: adenocarcinoma; LCC: large cell carcinoma.

Berberine as a Potential Anticancer Agent: A Comprehensive Review.

Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.

Decoding Clozapine-Induced Agranulocytosis: Unraveling Interactions and Mitigation Strategies.

Agranulocytosis represents a severe complication associated with the administration of clozapine. Clozapine is an antipsychotic medication that has demonstrated substantial efficacy in remediating refractory schizophrenia and various other psychiatric disorders. Nonetheless, it is crucial to monitor patients for neutropenia regularly during clozapine therapy. Therefore, this article aimed to delve into the prevalence of agranulocytosis during clozapine treatment by scrutinizing the extant literature to discern trends and correlations. This review endeavored to explore factors such as drug interactions, dose-related factors, duration of treatment, and genetic predispositions that could potentially influence the likelihood of patients developing agranulocytosis while undergoing clozapine therapy. Moreover, this review enunciates the ramifications of agranulocytosis on both patients and healthcare providers and meticulously evaluates the strategies to mitigate this risk and ensure optimal patient outcomes.

Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy.

3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1. The primary hits were selected based on their physicochemical, ADMET, and drug-like properties. Then, the binding affinities were calculated and analyzed the interactions to identify safer and more effective hits. The research identified two phytochemicals, Guggulsterone and Corylin, that exhibited significant affinity and specific interaction with the ATP-binding pocket of PAPSS1. Structural observations made by molecular docking were further accompanied by molecular dynamics (MD) simulations and principal component analysis (PCA) to examine the conformational changes and stability of PAPSS1 with the elucidated compounds Guggulsterone and Corylin. MD simulation results suggested that the binding of Guggulsterone and Corylin stabilizes the PAPSS1 structure, leading to fewer conformational changes. This implies that these compounds may be useful in developing PAPSS1 inhibitors for the therapeutic development against non-small cell lung cancer (NSCLC). This study highlights the potential of phytochemicals as PAPSS1 inhibitors and the utility of computational approaches in drug discovery.Communicated by Ramaswamy H. Sarma.

From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from Genus Artemisia.

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and natureinspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

Synthesis, Characterization, Antioxidant, and Anticancer Activity against Colon Cancer Cells of Some Cinnamaldehyde-Based Chalcone Derivatives.

The purpose of the current investigation was to produce cinammaldehyde-based chalcone derivatives (3a-k) to evaluate their potential effectiveness as antioxidant and inhibitory agents versus human Caco-2 cancer cells. The findings obtained using the DPPH assay showed that compound 3e had the highest effective antioxidant activity with the best IC50 value compared with the other compounds. Moreover, the cytotoxic findings revealed that compound 3e was the best compound for inhibiting Caco-2 development in contrast to all other produced derivatives, with the lowest IC50 concentration (32.19 ± 3.92 µM), and it also had no detrimental effects on healthy human lung cells (wi38 cells). Exposure of Caco-2 cells with this IC50 value of compound 3e resulted in a substantial rise in the number of early and late cells that are apoptotic with a significant comet nucleus when compared with control cells employing the annexin V/PI and comet evaluations, respectively. Furthermore, qRT-PCR and ELISA examinations indicated that compound 3e significantly altered the expression of genes and their relative proteins related to apoptosis in the treated Caco-2 cells, thus significantly inhibiting Caco-2 growth through activating Caspase-3 via an intrinsic apoptotic pathway. As a result, compound 3e could serve as an effective therapy for human colon cancer.