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Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.

Medicinal plants have been considered as potential source of therapeutics or as starting materials in drugs formulation. The current study aims to shed light on the therapeutic potential of the and Fruits by analyzing the phytochemical composition of their seeds and fruits using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to determine the presence of bioactive components such as flavonoids, phenols, vitamins, steroids, and essential oils. The protein content is usually higher than the total lipids in both species except the fruit of which contain more lipids than proteins. The total protein contents for were 235.03 ± 21.49 and 227.49 ± 25.82 mg/g dry weight while for were 201.9 ± 37.79 and 294.99 ± 37.93 mg/g dry weight for seeds and fruit, respectively. The Carvacrol levels in is 20 times higher than that in . Lower levels of α-Thujene, Phyllanderenes, Ascaridole, and Pinocarvone were also observed in both species. According to DPPH (2,2-diphenylpicrylhydrazyl) assay, seed the extract of exhibited the highest antioxidant activity (78.26±9.27 %) followed by the seed extract of (68.21±2.56 %). Similarly, FRAP (Ferric Reducing Antioxidant Power) assay showed that the highest antioxidant activity was exhibited by the seed extract of the two species; 20.14±1.11 and 21.18±1.04 µmol trolox g-1 DW for and , respectively. In terms of anti-lipid peroxidation, relatively higher values were obtained for the fruit extract of (6.08±0.35) and the seed extract of (6.11±0.55). Ethanolic seed extracts of had the highest efficiency against four Gram-negative bacterial species which causes serious human diseases, namely , , , and . In addition, was also inhibited by the fruit extract of both and . For the seed extract of , large inhibition zones were formed against and the fungus . Finally, we have explored the mode of action of these plants by performing detailed molecular modeling studies and showed that the antimicrobial activities of these plants could be attributed to the high binding affinity of their bioactive compounds to bind to the active sites of the sterol 14-alpha demethylase and the transcriptional regulator MvfR. These findings demonstrate the two species extracts possess high biological activities and therapeutical values, which increases their potential value in a number of therapeutic applications.

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.

Probiotic bacteria can confer health benefits to the human gastrointestinal tract. Lactic acid bacteria (LAB) are candidate probiotic bacteria that are widely distributed in nature and can be used in the food industry. The objective of this study is to isolate and characterize LAB present in raw and fermented milk in Saudi Arabia. Ninety-three suspected LAB were isolated from thirteen different types of raw and fermented milk from indigenous animals in Saudi Arabia. The identification of forty-six selected LAB strains and their genetic relatedness was performed based on 16S rDNA gene sequence comparisons. None of the strains exhibited resistance to clinically relevant antibiotics or had any undesirable hemolytic activity, but they differed in their other probiotic characteristics, that is, tolerance to acidic pH, resistance to bile, and antibacterial activity. In conclusion, the isolates Lactobacillus casei MSJ1, Lactobacillus casei Dwan5, Lactobacillus plantarum EyLan2, and Enterococcus faecium Gail-BawZir8 are most likely the best with probiotic potentials. We speculate that studying the synergistic effects of bacterial combinations might result in a more effective probiotic potential. We suspect that raw and fermented milk products from animals in Saudi Arabia, especially Laban made from camel milk, are rich in LAB and have promising probiotic potential.

Soil contamination with cobalt (Co) negatively impacts plant growth and production. To combat Co toxicity, plant growth-promoting microorganisms for improving plant growth are effectively applied. To this end, unclassified haloarchaeal species strain NRS_31 (OL912833), belonging to Haloferax genus , was isolated, identified for the first time, and applied to mitigate the Co phytotoxic effects on maize plants. This study found that high Co levels in soil lead to Co accumulation in maize leaves. Co accumulation in the leaves inhibited maize growth and photosynthetic efficiency, inducing oxidative damage in the tissue. Interestingly, pre-inoculation with haloarchaeal species significantly reduced Co uptake and mitigated the Co toxicity. Induced photosynthesis improved sugar metabolism, allocating more carbon to defend against Co stress. Concomitantly, the biosynthetic key enzymes involved in sucrose (sucrose-P-synthase and invertases) and proline (pyrroline-5- carboxylate synthetase (P5CS), pyrroline-5-carboxylate reductase (P5CR)) biosynthesis significantly increased to maintain plant osmotic potential. In addition to their osmoregulation potential, soluble sugars and proline can contribute to maintaining ROS hemostasis. Maize leaves managed their oxidative homeostasis by increasing the production of antioxidant metabolites (such as phenolics and tocopherols) and increasing the activity of ROS-scavenging enzymes (such as POX, CAT, SOD, and enzymes involved in the AsA/GSH cycle). Inside the plant tissue, to overcome heavy Co toxicity, maize plants increased the synthesis of heavy metal-binding ligands (metallothionein, phytochelatins) and the metal detoxifying enzymes (glutathione S transferase). Overall, the improved ROS homeostasis, osmoregulation, and Co detoxification systems were the basis underlying Co oxidative stress, mitigating haloarchaeal treatment's impact.

The uniqueness and novelty of this study lies in the ability of Mentha longifolia leaves extract (MLLE) to synthesize bimetallic NPs (NPs) of zinc oxide and magnesium oxide as nanocomposite (ZnO/MgO NPs) for the first time. Medicinal plants extracts are a more environmentally friendly method of creating NPs than physical or chemical methods. The specific objectives of the research were employed this nanocomposite compared to plant extract as antibacterial, anti-diabetic, antioxidant agents. Also, the possibility of using this nanocomposite as plant stimulator for reducing saline water stress on economic plants to cope with the scarcity of freshwater in the agricultural sector. In comparison to nanocomposite, MLLE exhibited high inhibition zones 28 ± 0.1, 26 ± 0.2, 26 ± 0.1, 25 ± 0.2, 25 ± 0.1 and 24 ± 0.1 mm in medium inoculated by E. faecalis , E. coli , S. typh , M. circinelloid C. albicans , and S. aureus , respectively. It was shown from the DPPH data that ZnO/MgO NPs’ IC 50 value (52.55 ± 0.98 µg/mL) was lower than the extract’s (299.27 ± 1.59 µg/mL) when compared to ascorbic (195.15 ± 1.63 µg/mL). Compared to acarbose, ZnO/MgO NPs exhibited superior activity against α-Amylase inhibition percentage, as evidenced by their IC 50 value of 117.02 ± 0.56 µg/mL. In contrast to ZnO/MgO NPs, acarbose had a lower IC 50 value of 22.15 ± 0.76 µg/mL. ZnO/MgO NPs were added to the soil cultivated by cucumber plants (A pots experiment) at quantities of 0, 200, and 400 mg/kg. Bimetallic ZnO/MgO NPs, particularly at 200 ppm, improved the shoot and root lengths and fresh weight of shoot, but they also seemed to reduce the level stress indicator of MDA, H 2 O 2 , and antioxidant enzymes (peroxidase and polyphenol oxidase). As a result, ZnO/MgO NPs may be employed as a unique approach to boost plant growth under salinity stress.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.Graphical Abstract

Biopolymers embedded with nanoparticles of metal oxides (MOs) demonstrate a wide range of bio-functions. Chitosan-incorporated MOs are an interesting class of support matrices for enhancing the biological function, compared to other support matrices. Therefore, the importance of this study lies in exploiting chitosan as a carrier not of one metal as in previous studies, but of two metals in the form of a nanocomposite to carry out several biological functions. The coprecipitation approach was employed to synthesize chitosan/Fe2O3/ZnO-nanocomposite in the present research. The characterization of chitosan/Fe2O3/ZnO-nanocomposite was performed to find out the morphology and dispersion properties of chitosan/Fe2O3/ZnO-nanocomposite. The X-ray diffraction (XRD) investigation revealed that these were crystalline. Fourier transforms infrared (FTIR) spectrum bands were viewed at 400/cm and 900/cm, due to the stretching vibration of Fe and Zn oxygen bond. TEM showed that chitosan/Fe2O3/ZnO-nanocomposite was of 20–95 nm in size. chitosan/Fe2O3/ZnO-nanocomposite exhibited inhibitory potential against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Candida albicans with inhibition zones of 25 ± 0.1, 28 ± 0.2, 27 ± 0.1, and 27 ± 0.2 mm, respectively while didn’t inhibited Aspergillus niger. MIC value of nanocomposite was 15.62 ± 0.33 µg/mL for C. albicans, B. subtilis and E. coli, while it was 62.50 ± 0.66 µg/mL for Pseudomonas aeruginosa. Ranged values of nanocomposite MBC (15.62 ± 0.33 to 125 ± 1 µg/mL) were attributed to all tested bacteria. Different concentrations of chitosan/Fe2O3/ZnO-nanocomposite MBC (25, 50, and 75%) reflected anti-biofilm activity against E. coli (85.0, 93.2, and 96.0%), B. subtilis (84.88, 92.21, and 96.99%), S. aureus 81.64, 90.52, and 94.64%) and P. aurogenosa (90.11, 94.43, and 98.24%), respectively. The differences in the levels of antimicrobial activities may depend on the type of examined microbes. Antioxidant activity of chitosan/Fe2O3/ZnO-nanocomposite was recorded with excellent IC50 values of 16.06 and 32.6 µg/mL using DPPH and ABTS scavenging, respectively. Wound heal by chitosan/Fe2O3/ZnO-nanocomposite was achieved with 100% compared to the untreated cells (76.75% of wound closer). The cytotoxicity outcomes showed that the IC50 of the chitosan/Fe2O3/ZnO-nanocomposite was 564.32 ± 1.46 µg/mL normal WI-38 cells. Based on the achieved findings, the chitosan/Fe2O3/ZnO-nanocomposite is a very promising agent for perform pharmacological activities.

The latest advancements in cellulose and its derivatives are the subject of this study. We summarize the characteristics, modifications, applications, and properties of cellulose. Here, we discuss new breakthroughs in modified cellulose that allow for enhanced control. In addition to standard approaches, improvements in different techniques employed for cellulose and its derivatives are the subject of this review. The various strategies for synthetic polymers are also discussed. The recent advancements in polymer production allow for more precise control, and make it possible to make functional celluloses with better physical qualities. For sustainability and environmental preservation, the development of cellulose green processing is the most abundant renewable substance in nature. The discovery of cellulose disintegration opens up new possibilities for sustainable techniques. Based on the review of recent scientific literature, we believe that additional chemical units of cellulose solubility should be used. This evaluation will evaluate the sustainability of biomass and processing the greenness for the long term. It appears not only crucial to dissolution, but also to the greenness of any process.

There are a number of disorders that affect the gastrointestinal tract. Such disorders have become a global emerging disease with a high incidence and prevalence rates worldwide. Inflammatory and ulcerative processes of the stomach or intestines, such as gastritis, ulcers, colitis, and mucositis, afflict a significant proportion of people throughout the world. The role of herbal-derived medicines has been extensively explored in order to develop new effective and safe strategies to improve the available gastrointestinal therapies that are currently used in the clinical practice. Studies on the efficacy of propolis (a unique resinous aromatic substance produced by honeybees from different types of species of plants) are promising and propolis has been effective in the treatment of several pathological conditions. This review, therefore, summarizes and critiques the contents of some relevant published scientific papers (including those related to clinical trials) in order to demonstrate the therapeutic value of propolis and its active compounds in the treatment and prevention of gastrointestinal diseases.