Polyphenolic compounds, especially flavonoids, are known as the most common chemical class of phytochemicals, which possess a multiple range of health-promoting effects. Flavonoids are ubiquitous in nature. They are also present in food, providing an essential link between diet and prevention of several diseases.

Atherosclerosis is a chronic inflammatory disease of the artery wall associated with lipid metabolism imbalance and maladaptive immune response, which mediates most cardiovascular events. First-line drugs such as statins and antiplatelet drug aspirin have shown good effects against atherosclerosis but may lead to certain side effects. Thus, the development of new, safer, and less toxic agents for atherosclerosis is urgently needed. Diosgenin and its analogs have gained importance for their efficacy against life-threatening diseases, including cardiovascular, endocrine, nervous system diseases, and cancer. Diosgenin and its analogs are widely found in the rhizomes of Dioscore, Solanum, and other species and share similar chemical structures and pharmacological effects. Recent data suggested diosgenin plays an anti-atherosclerosis role through its anti-inflammatory, antioxidant, plasma cholesterol-lowering, anti-proliferation, and anti-thrombotic effects. However, a review of the effects of diosgenin and its natural structure analogs on AS is still lacking. This review summarizes the effects of diosgenin and its analogs on vascular endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, migration and calcification, lipid metabolism, and inflammation, and provides a new overview of its anti-atherosclerosis mechanism. Besides, the structures, sources, safety, pharmacokinetic characteristics, and biological availability are introduced to reveal the limitations and challenges of current studies, hoping to provide a theoretical basis for the clinical application of diosgenin and its analogs and provide a new idea for developing new agents for atherosclerosis.

Skin cells can respond to UVB-induced damage either by tolerating it, or restoring it through antioxidant activation and DNA repair mechanisms or, ultimately, undergoing programmed cell death, when damage is massive. Nutritional factors, in particular, food antioxidants, have attracted much interest because of their potential use in new preventive, protective, and therapeutic strategies for chronic degenerative diseases, including skin inflammation and cancer. Some polyphenols, present in virgin olive oil, well tolerated by organism after oral administration, show a variety of pharmacological and clinical benefits such as anti-oxidant, anti-cancer, anti-inflammatory, and neuro-protective activities. Here, the protective effects of antioxidant compounds against UV-induced apoptosis have been described in HaCat cell line. Human keratinocytes were pre-treated with antioxidants before UVB exposure and their effects have been evaluated by means of ultrastructural analyses. After UVB radiation, a known cell death trigger, typical apoptotic features, absent in control condition and in antioxidant alone-treated cells, appear. An evident numerical decrease of ultrastructural apoptotic patterns and TUNEL positive nuclei can be observed when natural antioxidants were supplied before cell death induction. These data have been confirmed by molecular investigation of caspase activity. In conclusion, this paper highlights antioxidant compound ability to prevent apoptotic cell death in human keratinocytes exposed to UVB, suggesting, for these molecules, a potential role in preventing skin damage.

The aim of this study was to develop smart materials with stimuli-responsive properties for the long-term protection of steel. The idea was to obtain a tailored and controlled release of protective agents in response to the environment stimuli. First, the protective efficacy of three inhibitors containing a carboxylic moiety, such as p-aminobenzoic (pAB), succinic (SA), and caffeic (CA) acids, was investigated in alkaline chloride solutions. The results revealed that pAB is the most effective protective agent, significantly better than SA and CA. It is surprising that the steel surface in the pAB solution remains unchanged even after 5 months of corrosion treatment, whereas the formation of degradation products in the SA and CA solutions was observed after only 6 days. Based on these findings, pAB was selected and used for the functionalization of silica nanoparticles and layered double hydroxides (LDHs) that can act as delivery vehicles and as an inhibitor reservoir. Specifically, pAB was chemisorbed on silica amino groups via an amide bond, and this makes possible a gradual inhibitor release induced by an alkaline environment. The intercalation of pAB in its anionic form into the LDHs structure is responsible for a completely different behavior since the release is induced by chloride ions and occurs by an anionic exchange reaction. Thus, these materials play a dual role by acting as an inhibitor reservoir and by capturing chlorides. These findings reveal that it is possible to create a reservoir of corrosion inhibitors gradually released on demand based on the chemical environment. The stimuli-responsive properties and the complementary protective action of inhibitor-loaded silica and LDHs make them attractive for the long-term protection of steel and open the way for innovative solutions in the preservation of concrete cultural heritage.

The purpose of this in vitro study was to evaluate the preventive effects of different protective agents on dentine erosion, measuring mean percentage weight loss. Dissolution of dentine under erosive challenges caused by soft drinks was analyzed: specimens were weighed following each immersion period, with mean percent weight losses calculated.

Sulfur mustard (SM) and its derivatives are potent genotoxic agents, which have been shown to trigger the activation of poly (ADP-ribose) polymerases (PARPs) and the depletion of their substrate, nicotinamide adenine dinucleotide (NAD+). NAD+ is an essential molecule involved in numerous cellular pathways, including genome integrity and DNA repair, and thus, NAD+ supplementation might be beneficial for mitigating mustard-induced (geno)toxicity. In this study, the role of NAD+ depletion and elevation in the genotoxic stress response to SM derivatives, i.e., the monofunctional agent 2-chloroethyl-ethyl sulfide (CEES) and the crosslinking agent mechlorethamine (HN2), was investigated with the use of NAD+ booster nicotinamide riboside (NR) and NAD+ synthesis inhibitor FK866. The effects were analyzed in immortalized human keratinocytes (HaCaT) or monocyte-like cell line THP-1. In HaCaT cells, NR supplementation, increased NAD+ levels, and elevated PAR response, however, did not affect ATP levels or DNA damage repair, nor did it attenuate long- and short-term cytotoxicities. On the other hand, the depletion of cellular NAD+ via FK866 sensitized HaCaT cells to genotoxic stress, particularly CEES exposure, whereas NR supplementation, by increasing cellular NAD+ levels, rescued the sensitizing FK866 effect. Intriguingly, in THP-1 cells, the NR-induced elevation of cellular NAD+ levels did attenuate toxicity of the mustard compounds, especially upon CEES exposure. Together, our results reveal that NAD+ is an important molecule in the pathomechanism of SM derivatives, exhibiting compound-specificity. Moreover, the cell line-dependent protective effects of NR are indicative of system-specificity of the application of this NAD+ booster.

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO. The anti-inflammatory activity of 14 target compounds was studied on isolated primary murine macrophages after LPS stimulation. Seven compounds were identified to inhibit the synthesis of nitric oxide and interleukin 6 at a concentration of 100 µM. The most active compounds are micromolar inhibitors of IL-6 secretion and NO synthesis, showing a minimal impact on innate immunity, unlike the reference drug dexamethasone, along with acceptable cytotoxicity. Evaluation in an animal model of acute lung injury proved the protective activity of compound 6e, which was supported by biochemical, cytological and morphological markers.

Human breast milk (HBM)-derived exosomes contain various biological and immunological components. However, comprehensive immune-related and antimicrobial factor analysis requires transcriptomic, proteomic, and multiple databases for functional analyses, and has yet to be conducted. Therefore, we isolated and confirmed HBM-derived exosomes by detecting specific markers and examining their morphology using western blot and transmission electron microscopy. Moreover, we implemented small RNA sequencing and liquid chromatography-mass spectrometry to investigate substances within the HBM-derived exosomes and their roles in combating pathogenic effects, identifying 208 miRNAs and 377 proteins associated with immunological pathways and diseases. Integrated omics analyses identified a connection between the exosomal substances and microbial infections. In addition, gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that HBM-derived exosomal miRNA and proteins influence immune-related functions and pathogenic infections. Finally, protein-protein interaction analysis identified three primary proteins (ICAM1, TLR2, and FN1) associated with microbial infections mediating pro-inflammation, controlling infection, and facilitating microbial elimination. Our findings determine that HBM-derived exosomes modulate the immune system and could offer therapeutic strategies for regulating pathogenic microbial infection.

Dose-limiting toxicities for cisplatin administration, including ototoxicity and nephrotoxicity, impact the clinical utility of this effective chemotherapy agent and lead to lifelong complications, particularly in pediatric cancer survivors. Using a two-pronged drug screen employing the zebrafish lateral line as an in vivo readout for ototoxicity and kidney cell-based nephrotoxicity assay, we screened 1280 compounds and identified 22 that were both oto- and nephroprotective. Of these, dopamine and L-mimosine, a plant-based amino acid active in the dopamine pathway, were further investigated. Dopamine and L-mimosine protected the hair cells in the zebrafish otic vesicle from cisplatin-induced damage and preserved zebrafish larval glomerular filtration. Importantly, these compounds did not abrogate the cytotoxic effects of cisplatin on human cancer cells. This study provides insights into the mechanisms underlying cisplatin-induced oto- and nephrotoxicity and compelling preclinical evidence for the potential utility of dopamine and L-mimosine in the safer administration of cisplatin.

Ecdysteroid-containing herbal extracts, commonly prepared from the roots of Cyanotis arachnoidea, are marketed worldwide as a "green" anabolic food supplement. Herein are reported the isolation and complete 1H and 13C NMR signal assignments of three new minor ecdysteroids (compounds 2-4) from this extract. Compound 4 was identified as a possible artifact that gradually forms through the autoxidation of calonysterone. The compounds tested demonstrated a significant protective effect on the blood-brain barrier endothelial cells against oxidative stress or inflammation at a concentration of 1 μM. Based on these results, minor ecdysteroids present in food supplements may offer health benefits in various neurodegenerative disease states.

The potential use of biological agents has become a major public health concern worldwide. According to the CDC classification, Bacillus anthracis and Clostridium botulinum, the bacterial pathogens that cause anthrax and botulism, respectively, are considered to be the most dangerous potential biological agents. Currently, there is no licensed vaccine that is well suited for mass immunization in the event of an anthrax or botulism epidemic. In the present study, we developed a dual-expression system-based multipathogen DNA vaccine that encodes the PA-D4 gene of B. anthracis and the HCt gene of C. botulinum. When the multipathogen DNA vaccine was administered to mice and guinea pigs, high level antibody responses were elicited against both PA-D4 and HCt. Analysis of the serum IgG subtype implied a combined Th1/Th2 response to both antigens, but one that was Th2 skewed. In addition, immunization with the multipathogen DNA vaccine induced effective neutralizing antibody activity against both PA-D4 and HCt. Finally, the protection efficiency of the multipathogen DNA vaccine was determined by sequential challenge with 10 LD50 of B. anthracis spores and 10 LD50 of botulinum toxin, or vice versa, and the multipathogen DNA vaccine provided higher than 50% protection against lethal challenge with both high-risk biothreat agents. Our studies suggest the strategy used for this anthrax-botulinum multipathogen DNA vaccine as a prospective approach for developing emergency vaccines that can be immediately distributed on a massive scale in response to a biothreat emergency or infectious disease outbreak. Key points • A novel multipathogen DNA vaccine was constructed against anthrax and botulism. • Robust immune responses were induced following vaccination. • Suggests a potential vaccine development strategy against biothreat agents.

Objectives: To evaluate and compare the effectiveness of resin- and varnish-based surface protective agents on Glass Ionomer Cement (GIC). The different surface protective agents used were: Vaseline®, GC Fuji VARNISH™ (varnish), G-Coat Plus™ (resin) and EQUIA® Coat (resin). Method: Thirty-six identical specimens of GIC were made. Six specimens were used in preparation of standard solution and remaining thirty were divided into five groups with six specimens in each group. Each test specimen was coated with one of the surface protecting agent except for the control group. The specimens were immersed separately into 1 ml of 0.05% methylene blue solution for 24 h and then rinsed with deionised water and further immersed into tubes containing 1 ml of 65% nitric acid. Specimens, once completely dissolved in nitric acid solution, were filtered and centrifuged. The supernatant was used to determine the absorbance using a spectrophotometer. The effectiveness of the surface protecting agents for the GIC was recorded in micrograms of dye per specimen, where low values indicate good protection. Result: Tukey HSD test revealed that GC Fuji VARNISH™ (varnish; mean = 21.25 µg/ml), G-Coat Plus™ (resin; mean = 30.39 µg/ml) and EQUIA® Coat (resin; mean = 9.32 µg/ml) were statistically not significantly different to each other and were effective in protecting the surface of GIC. Significance: The study found that there was a statistically significant difference between control and GC Fuji VARNISH™, G-Coat Plus™ and EQUIA® Coat. The three agents were found to be equally effective in protecting the surface of GIC.

Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models.

The phenothiazine derivatives, tricyclic 10H-3,6-diazaphenothiazine (DPT-1) and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine (DPT-2), have recently been shown to exhibit promising anticancer activities in vitro. In this report, we demonstrated that DPT-1 and DPT-2 could be pro-apoptotic agents in lung carcinoma, the human lung carcinoma A549 and non-small lung carcinoma H1299, in the range of IC50 = 1.52-12.89 µM, with a protective potential to healthy cell lines BEAS-2B and NHDF. The compounds showed higher activity in the range of the tested concentrations and low cytotoxicity in relation to normal healthy cells than doxorubicin, used as the reference drug. The cytostatic potential of DPT-1 and DPT-2 was demonstrated with the use of MTT assay. Cell cycle analysis via flow cytometry using Annexin-V assay showed the pro-apoptotic and pro-necrotic role of the studied diazaphenothiazines in the cell cycle. DPT-1 and DPT-2 initiated a biological response in the investigated cancer models with a different mechanism and at a different rate. Based on these findings, it can be concluded that DPT-1 and DPT-2 have potential as chemotherapeutic agents.

Onion (Allium cepa) is a member of the family Amaryllidaceae and one of the most widely cultivated species of the genus Allium. Onion has plentiful chemical compounds such as allicin, quercetin, fisetin, other sulphurous compounds: diallyl disulphide and diallyl trisulphide. Onion and its main components in specific doses have shown a lot of benefits including free-radical scavenging and antioxidant properties, anticholesterolemic, anti-heavy metals toxicity, antihyperuricemia, antimicrobial, anti-gastric ulcer, and anticancer. This study summarizes numerous in-vitro and animal studies on the protective effects of onion against natural and chemical toxicities. Onion and its main components can ameliorate the toxicity of chemical agents in kidney, liver, brain, blood, heart, reproductive system, embryo, pancreas through reducing lipid peroxidation, antioxidant effect, radical-scavenging, anti-inflammatory, chelating agent, cytoprotective activities, increasing protein synthesis in damaged tissues, suppressing apoptosis, as well as modulation of PKC-𝜀/p38MAPK, Wnt/beta-Catenin, ERK, JNK, p38 MAPK, Bcl-2, Bax, and NF-κB signaling pathways.

TRH (thyroliberin) and its analogues were reported to possess neuroprotective effects in cellular and animal experimental models of acute and chronic neurodegenerative diseases. In the present study we evaluated effects of TRH and its three stable analogues, montirelin (CG-3703), RGH-2202 and Z-TRH (N-(carbobenzyloxy)-pGlutamyl-Histydyl-Proline) on the neuronally differentiated human neuroblastoma SH-SY5Y cell line, which is widely accepted for studying potential neuroprotectants. We found that TRH and all the tested analogues at concentrations 0.1-50 μM attenuated cell damage induced by MPP(+) (2 mM), 3-nitropropionate (10 mM), hydrogen peroxide (0.5 mM), homocysteine (250 μM) and beta-amyloid (20μM) in retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the staurosporine (0.5 μM)-induced LDH release, caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these peptides. The neuroprotective effects of TRH (10 μM) and RGH-2202 (10 μM) on St-induced cell death was attenuated by inhibitors of PI3-K pathway (wortmannin and LY294002), but not MAPK/ERK1/2 (PD98059 and U0126). Moreover, TRH and its analogues at neuroprotective concentrations (1 and 10 μM) increased expression of Bcl-2 protein, as confirmed by Western blot analysis. All in all, these results extend data on neuroprotective properties of TRH and its analogues and provide evidence that mechanism of anti-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3K/Akt pathway and Bcl-2. Furthermore, the data obtained on human cell line with a dopaminergic phenotype suggest potential utility of TRH and its analogues in the treatment of some neurodegenerative diseases including Parkinson's disease.

Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.

Does LH protect mouse oocytes and female fertility from alkylating chemotherapy?

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1-50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5-10 mg/kg) and INV-161 (1-10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.