Search

Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration. [ABSTRACT FROM AUTHOR]

In the context of designing innovative anticancer agents, the synthesis of a series of chalcones bearing a 3,4,5-trimethoxylated A ring and a variety of B rings, including phenols and original heterocycles such as chromones, was conducted. For this end, Claisen–Schmidt condensation was performed in basic or acidic conditions between the common starting material 3,4,5-trimethoxyacetophenone and appropriate aldehydes; this allowed the recovery of fifteen chalcones in moderate–good yields. The synthesized compounds were screened for their antiproliferative activity against colorectal and prostatic cancer cells, using a colorimetric MTT assay. Among the new chromonyl series, chalcone 13 demonstrates an interesting antiproliferative effect, with IC50 values in the range of 2.6–5.1 µM at 48 h. Then, our study evidenced that indolyl chalcone 10 exhibits excellent activity towards the selected cell lines (with IC50 less than 50 nM). This compound has already been described and has been shown to be a potent anticancer agent against other cancer cell lines. Our investigations highlighted apoptosis induction, through several pro-apoptotic markers, of these two heterocyclic chalcones. Considering phenolic chalcones, compounds 2 and 8 were found to be the most active against cell proliferation, exerting their effect by inducing the depolymerization of cell microtubules. The most promising compounds in this series will be selected for application in a strategy of vectorization by either active or passive targeting. [ABSTRACT FROM AUTHOR]

Skin cancer is the most widespread type of malignant tumor representing a major public health concern. Considering the numerous side effects associated with conventional treatments, phytotherapy may be regarded as a viable medicinal alternative. This study aimed to investigate the therapeutic potential of Orbea variegata (L.) Haw, an ornamental plant, in treating skin cancer using an animal model induced by a combination of ultraviolet (UV) irradiation and sulfuric acid treatment. The hydroethanolic extract of Orbea variegata underwent phytochemical characterization, identifying the presence of reducing sugars, coumarins, alkaloids, flavonoids, tannins, and saponins through qualitative screening. Quantitative analysis demonstrated significant amounts of phenolic compounds (29.435 ± 0.571 mg GAE/g of dry extract), flavonoids (6.711 ± 0.272 mg QE/g of dry extract), and tannins (274.037 ± 11.3 mg CE/g of dry extract). The administration the hydroethanolic extract in two concentrations (1 or 2 g/kg) to male Swiss mice exhibited no marked adverse effects, as evidenced by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activity levels. In addition, the extract significantly reduced skin hyperplasia and inflammation induced by UV/sulfuric acid treatment as noted in tissue analyses and decreased protein expression of nuclear proliferation marker (Ki-67). This improvement was associated with a marked decrease in oxidative stress, as indicated by diminished lipid peroxidation levels, and restoration of the activity of endogenous antioxidant enzyme catalase (CAT) to control levels. Our findings demonstrated the potential of Orbea variegata hydroethanolic extract to be considered as a treatment for skin cancer, exhibiting its apparent safety and efficacy in reducing inflammation and carcinogenesis in a UV/sulfuric acid-induced Swiss mouse model, attributed to its phytochemical content and associated antioxidant activities. [ABSTRACT FROM AUTHOR]

This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 μm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki‐67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure. [ABSTRACT FROM AUTHOR]

Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases. [ABSTRACT FROM AUTHOR]

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/β-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies. [ABSTRACT FROM AUTHOR]

Platelets were isolated from healthy donors (n = 10, green dots), COVID-19 patients treated with aspirin (n = 10, red dots), or not treated with aspirin (n = 10, blue squares). Given that aspirin was found without effect on platelet functions in certain proinflammatory conditions, [15][16][27] and since it is unclear what mediates platelet activation in COVID-19, the question of whether aspirin would have any effect on platelet activation in COVID-19 patients remained to be addressed. Thus, an aspirin regimen can reduce platelet aggregation induced by low concentrations of thrombin and collagen and the production of TxB SB 2 sb , but the effects of aspirin on platelet aggregation are lost with higher concentrations of agonists. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is spreading throughout the world at an alarming rate. [Extracted from the article]

The accurate assessment of hormone receptors, HER2, and Ki-67 proliferative index provides meaningful information about breast cancer prognosis and prediction of therapy response. Immunohistochemistry, the most common method for evaluating these prognostic biomarkers, can be impacted by numerous variabilities due to preanalytical/analytical factors and subjective interpretation by pathologists. The Xpert® Breast Cancer STRAT4, an RT-qPCR based system, can be used to classify invasive breast carcinomas based on the assessment of these four biomarkers; Methods: We evaluated ESR1, PGR, ERBB2, and MKi67 mRNA expression by Xpert Breast Cancer STRAT4 and ER, PR, HER2 and Ki67 by IHC (FISH for HER2 IHC 2+) in 200 formalin-fixed paraffin-embedded (FFPE) tissue blocks with invasive breast cancer, collected from the Pathology Department of Casablanca Ibn Rochd University Hospital; Results: Concordance between Xpert ® Breast Cancer STRAT4 and IHC was 93.5% for ER, 83.51% for PR, 95% for HER2 (92% for IHC+FISH), and 81.20% for Ki67 (excluding intermediate IHC Staining 10 ≤ %IHC <20). The simple Kappa coefficient was, for ER, 0.830 (P < 0.0001), 0.565 (P < 0.0001) for PR, 0.838 (P < 0.0001) for HER2-IHC, 0.771 (P < 0.0001) for HER2 IHC+FISH and, for, Ki67, 0.458 (P < 0.0001); Conclusions: We demonstrated globally a high concordance between centrally assessed IHC, IHC+FISH and mRNA measurements of ER/ESR1 and HER2/ERBB2, and a moderate agreement between PR/PGR and Ki67/MKi67. These findings provide an additional, objective, and quantitative assessment of tumor receptor status in breast cancer. [ABSTRACT FROM AUTHOR]

To further explore the signaling mechanism involved in the regulatory role of PKC in thrombin-induced platelet aggregation in CD patients, we assessed the phosphorylation of PKC on Tyr SP 311 sp and Thr SP 505 sp . In human platelets, pre-treatment with the specific PKC inhibitor significantly decreased platelet activation in patients with CD. The pathogenesis of inflammatory bowel diseases (IBD), representing chronic and relapsing-remitting disorders of the gastrointestinal tract, encompasses Crohn's disease (CD) and ulcerative colitis. [Extracted from the article]

Background: Artemisia herba-alba (AHA) is largely used in folk medicine in different countries. However, rare studies provided toxicological evaluation regarding their safety on human health. Objective: This study investigated the safety of the standardized aqueous extract of AHA, like used by patients, to evaluate their toxicity in vivo and in vitro. Materials and Methods: For toxicological evaluation in vivo we used acute (during 14 days) and sub-acute oral gavages in Wistar rats (rats treated daily for 42 days at 1-5 g/kg bw) and the 3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was performed to determine the level of cell viability and the degree of cytotoxicity in vitro (0-30 µg/ml) on cultured spleen cells. Results: The LD50 was up to 2 g/kg. Signs of mortality and toxicity were observed after single doses and no-observed-adverse-effect levels in the sub acute toxicity was up to 2 g/kg bw. Compared to the control, the treatment did not produce any statistically significant changes on alanine aminotransferase and aspartate aminotransferase serum titer. However, for creatinine and urea serum value, a significant increase (P < 0.05) was observed. The histological observations of liver and spleen tissues have shown well-preserved normal cells. Indeed for kidney tissues some artifacts of retraction and vascular congestion were noted for 3-5 g/kg doses after sub-chronic treatment. The addition of plant extracts to the spleen cells did not show any sign of toxicity for all doses tested. Conclusion: We conclude that AHA aqueous extract at the dosage up to 2g/kg bw will be toxic and can affect mainly the kidney tissues. [ABSTRACT FROM AUTHOR]

[13] Although platelets from COVID-19 patients have shown hyperreactivity, [4][5][6] no scientific data have been able to demonstrate platelet dysfunction in people injected with the Oxford-AstraZeneca vaccine. [13] Therefore, this study aimed to assess platelet function by measuring the aggregation of platelets from participants who had been injected with the Oxford-AstraZeneca vaccine compared with platelets from a cohort of healthy donors. [Extracted from the article]

Background: Artemisia herba-alba (AHA) is largely used in folk medicine in different countries. However, rare studies provided toxicological evaluation regarding their safety on human health. Objective: This study investigated the safety of the standardized aqueous extract of AHA, like used by patients, to evaluate their toxicity in vivo and in vitro. Materials and Methods: For toxicological evaluation in vivo we used acute (during 14 days) and sub-acute oral gavages in Wistar rats (rats treated daily for 42 days at 1-5 g/kg bw) and the 3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was performed to determine the level of cell viability and the degree of cytotoxicity in vitro (0-30 µg/ml) on cultured spleen cells. Results: The LD50 was up to 2 g/kg. Signs of mortality and toxicity were observed after single doses and no-observed-adverse-effect levels in the sub acute toxicity was up to 2 g/kg bw. Compared to the control, the treatment did not produce any statistically significant changes on alanine aminotransferase and aspartate aminotransferase serum titer. However, for creatinine and urea serum value, a significant increase (P < 0.05) was observed. The histological observations of liver and spleen tissues have shown well-preserved normal cells. Indeed for kidney tissues some artifacts of retraction and vascular congestion were noted for 3-5 g/kg doses after sub-chronic treatment. The addition of plant extracts to the spleen cells did not show any sign of toxicity for all doses tested. Conclusion: We conclude that AHA aqueous extract at the dosage up to 2g/kg bw will be toxic and can affect mainly the kidney tissues. [ABSTRACT FROM AUTHOR]