In recent years, essential oils have attracted wide attention because of their extensive applications in biomedical products, pharmaceutical preparations, and treating various human diseases, particularly for cancer therapy and as an option to find novel chemical entities as promising anticancer drugs. In this study, we evaluated the cytotoxic effects of Lippia citriodora essential oils on human breast cancer cells (MCF-7) and investigated their potential mechanism of action, focusing on apoptosis/necrosis induction and the modulation of p53, Bcl-2/Bax, and c-Jun gene transcription. The cytotoxic activity was assessed on MCF-7 breast adenocarcinoma cells using the MTT assay. Apoptotic effects were further examined through DNA fragmentation analysis and Annexin V-biotin streptavidin FITC/propidium iodide staining. In addition, changes in the relative mRNA expression levels of p53, Bcl-2, Bax, and c-Jun genes were analyzed using RT-qPCR. The results revealed a potent dose-dependent cytotoxic effect of the essential oil on MCF-7 cells, with IC50 values ranging from 34.72 to 70.75 mu g/mL. Furthermore, essential oil-treated MCF-7 cells exhibited characteristics of late apoptosis and necrosis. Gene expression analysis showed a significant upregulation of Bax, Bcl-2, p53, and c-Jun transcripts 12 h posttreatment. Overall, these findings suggest that the essential oil induces cell death primarily through necrosis and late apoptosis, potentially by targeting cellular DNA and upregulating key apoptosis-related genes.

Leukemia constitutes approximately one-third of all pediatric cancers, with acute lymphoblastic leukemia (ALL) comprising roughly 80% of pediatric leukemia instances. This study sought to ascertain the prevalence of HLA A, B, DR, and DQ allele groups linked with pediatric acute leukemia. We recruited 70 Moroccan children diagnosed with acute lymphoblastic leukemia (ALL), 39 of whom had BCP-ALL and were eligible for hematopoietic stem cell transplantation, compared to a control group of 136 healthy children. Patients and controls were subjected to HLA class I and II typing, utilizing either sequence-specific primers (SSPs) or sequence-specific oligonucleotides (SSOs) in polymerase chain reaction-based techniques. The findings indicated significantly elevated frequencies of HLA-A*68 and B*14 in pediatric patients with ALL relative to the control group (p = 0.001 and p = 0.02, respectively). The frequencies of HLA-DRB1*01 and DQB1*05 allele groups were considerably elevated in children with ALL and BCP-ALL compared to the controls (p < 0.01 for both). The findings of our study indicate that HLA-A*68, -B*14, -DRB1*01, and DQB1*05 may serve as potential predisposing immunogenetic variables for the development of juvenile acute lymphoblastic leukemia (ALL). Nonetheless, additional research including a bigger sample considering other regions of Morocco would be beneficial to more accurately delineate the association between the HLA system and ALL.

Moringa oleifera, widely recognized as the horseradish tree or drumstick tree, is classified within the Moringaceae family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of Moringa oleifera and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of Moringa oleifera, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant's effect on the immune response via different pathways. Several studies indicate that Moringa oleifera mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that Moringa oleifera can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8+ and CD4+ T lymphocytes. Together, Moringa oleifera could be considered for the treatment of conditions related to immune dysregulation, such as cancer.

Background/Objectives: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with over 50% of individuals succumbing to the disease annually. This study aimed to assess the correlation between human leukocyte antigen (HLA) genes and acute myeloid leukemia (AML) in an adult Moroccan cohort. We included 60 persons with acute myeloid leukemia (AML) who were eligible for hematopoietic stem cell transplantation and compared them to a control group of 90 healthy adults. Methods: Patients and controls were subjected to HLA class I and II typing utilizing either sequence-specific primers (SSP) or sequence-specific oligonucleotides (SSO) in polymerase chain reaction-based methodologies. Results: The AML categories were predominantly represented by AML2, AML3, and AML4, comprising 36.66%, 30%, and 16.66%, respectively. We identified a notable correlation between HLA-A*11 (p = 0.003) and HLA-B*27 (p = 0.005) with acute myeloid leukemia (AML), and for HLA class II allele groups, we detected an elevated frequency of HLA-DQB1*05 (p = 0.002) in adult AML patients. We identified a notable correlation between AML 2 and the allele groups examined, namely with HLA class I: HLA-A*11 (p = 0.0003) and HLA-B*27 (p = 0.00006). Conclusion: Our study suggests a potential association between specific HLA alleles and the development of AML specifically AML type 2 in adults. Further larger studies are needed to confirm these findings.

To evaluate the anti-tumoral and antioxidant capacities of clove buds essential oils from Indonesia, Comoros Islands and India, we conducted the MTT test, along with various antioxidant capacity assessments, including evaluations of ferrous ions (Fe2+) chelating activity, ammonium molybdate test (TAC), reducing power assay (FRAP), TBARS assay, DPPH, ABTS+ tests, and (3-Carotene Bleaching Assay. All examined essential oils displayed significant antioxidant activity in various conducted tests. Moreover, these essential oils have demonstrated strong in vitro cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7) and a mouse mastocytoma cell line (P815). Importantly, they have shown the ability to preserve the integrity of healthy cells; specifically peripheral blood mononuclear cells. The chemical composition of the studied essential oils showed that Eugenol, Caryophyllene, and Humulene percentages were notably higher in the Indonesian and Indian samples compared to the Comorian sample. However, the Comorian sample uniquely contained isoeugenol (55.45%), levomenthol (13.39%), eucalyptol (13.30%), and Thymol, which were absent in the Indonesian and Indian samples. The variations in chemical profiles among essential oils from different geographical origins are responsible for the observed differences in antioxidant and cytotoxic activities.

In this study, a new family of ethacrynic acid-sulfonamides and indazole-sulfonamides was synthesized and tested in vitro against MDA-MB-468 triple-negative breast cancer cells and PBMCs human peripheral blood mononuclear cells, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The aim of this research is to discover novel compounds with potential therapeutic effects on breast cancer. The antiproliferative activity of these compounds showed a significant dose-dependent activity, with IC50 values ranging between 2.83 and 7.52 µM. The lead compounds 8 and 9 displayed similar IC50 values to paclitaxel with 2.83, 3.84 and 2.72 µM, respectively. This highlights the novelty and potential of these compounds as alternatives to current treatments. The binding properties of 8, 9, and paclitaxel with the active sites of the PARP1(Poly(ADP-ribose) polymérase 1) and EGFR (Epidermal growth factor receptor) proteins were analyzed by molecular docking methods showing, for PARP1 protein, binding affinities of -9.8 Kcal /mol, -10 Kcal /mol, and -9.4 Kcal /mol, respectively. While their binding affinities for EGFR protein are -7.5 Kcal/mol, -7.2 Kcal/mol and -6.9 Kcal/mol, respectively. Moreover, drug-likeness and ADMET (Absorption-distribution-metabolism-excretion-toxicity) analyses demonstrated that both molecules are orally bioavailable and have good pharmacokinetic and non-toxic profiles. DFT (Density functional theory) was also carried out on both compounds 8 and 9 additionally to POM (Petra/Osiris/Molinspiration) studies on all compounds. The outcomes of this study suggest that compounds 8 and 9 are promising candidates for further development as therapeutic agents against triple-negative breast cancer.

AbstractThis study aimed to explore the antioxidant potential of the ethyl acetate extract of Streptomyces coeruleofuscus SCJ strain, along with its inhibitory effects on the triple-negative human breast carcinoma cell line (MDA-MB-468). The ethyl acetate extract’s total phenolic and flavonoid contents were quantified, and its antioxidant activity was investigated using DPPH (1,1-Diphenyl-2-picrylhydrazyl), ABTS (2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), and FRAP (Ferric Reducing Antioxidant Power) assays. Furthermore, the cytotoxic effect of the organic extract from Streptomyces coeruleofuscus SCJ on MDA-MB-468 cancer cells was assessed via the crystal violet assay. In tandem, a thorough computational investigation was conducted to explore the pharmacokinetic properties of the identified components of the extract, utilizing the SwissADME and pKCSM web servers. Additionally, the molecular interactions between these components and Estrogen Receptor Beta, identified as a potential target, were probed through molecular docking studies. The results revealed that ethyl acetate extract of SCJ strain exhibited remarkable antioxidant activity, with 39.899 ± 1.56% and 35.798 ± 0.082% scavenging activities against DPPH and ABTS, respectively, at 1 mg/mL. The extract also displayed significant ferric reducing power, with a concentration of 1.087 ± 0.026 mg ascorbic acid equivalents per mg of dry extract. Furthermore, a strong positive correlation (p < 0.0001) between the antioxidant activity, the polyphenol and the flavonoid contents. Regarding anticancer activity, the SCJ strain extract demonstrated significant anticancer activity against TNBC MDA-MB-468 cancer cells, with an inhibition percentage of 62.76 ± 0.62%, 62.67 ± 0.93%, and 58.07 ± 4.82% at 25, 50, and 100 µg/mL of the extract, respectively. The HPLC-UV/vis analysis revealed nine phenolic compounds: gallic acid, sinapic acid, p-coumaric acid, cinnamic acid, trans-fereulic acid, syringic acid, chloroqenic acid, ellagic acid, epicatechin. Streptomyces coeruleofuscus SCJ showed promise for drug discovery, exhibiting antioxidant and anticancer effects.

Hepatitis B virus (HBV) infection is a global public health burden and affects approximatively 300 million people around the world. Since, HBV population is represented with genetic diversity, having different viral effects. Development of a new prognosis method play a key role on the efficiency of the different treatment. The HBx protein of HBV has a potential role in Hepatocellular Carcinoma (HCC), which makes it a valuable target for HCC prognosis. In this context, the first quantitative real-time PCR (qRT-PCR) assay in the Mediterranean area was developed and validated. Specific primers and probes of a conserved X region across all HBV genotypes were designed and the qRT-PCR was performed with the TaqPath 1-Step Multiplex Master Mix on 441 Moroccan plasma samples in Pasteur Institute of Morocco. The assay demonstrated a linear quantification range of 1010-101 IU/reaction (R2 = 0.99) and a quantification limit of 15 IU/mL. Comparative evaluations with the COBAS Ampliprep/COBAS TaqMan (CAP/CTM) HBV, v2.0 and the artus HBV QS-RGQ assays showed strong correlations (R2 = 0.92 and R2 = 0.89, respectively). Our test is fast, highly sensitive, specific, reproducible, and labor-saving. This system will be of great advantage to Mediterranean countries in their efforts to eliminate viral hepatitis B and C by 2030, enabling precise monitoring and effective treatment of HBV infections.

In alignment with Morocco's national strategy for eliminating viral hepatitis, we aimed to characterize and update the virological profile of chronic hepatitis B patients. Demographic, serological and molecular parameters of 804 HBsAg-positive patients were retrospectively analyzed. Overall, 58.24% were HBV-positive (55.37% males, p=0.74). The median age was 46 years (37-57). Patients ≤24 years comprised 5% of HBsAg-positive and 4.34% of HBV-positive cases. The median viral load was 2.62 log10 IU/mL (1.87-3.44). The prevalent genotypes were D (91.04%), A (7.55%) and E (1.41%). Liver enzymes were normal in most of cases. 91.04% of patients were HBeAg-negative, with 92.23% having genotype D (p<0.001). Co-infection rates with other hepatitis viruses were low. Significant associations were found between HBeAg-negative status, genotype D, viral load, and liver enzyme levels (p<0.001). We highlighted the need for prenatal HBsAg screening for pregnant women and prioritizing the birth-dose vaccine to prevent mother-to-child transmission, especially after the COVID-19 pandemic.

IntroductionCOVID-19 is a viral infection that disturbs the host's immune system and causes an overproduction of cytokines leading to a cytokine storm. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with COVID-19 disease severity.MethodsThe serum levels of 89 patients with different degrees of COVID-19 disease severity [asymptomatic (n = 14), moderate (n = 14), severe (n = 30), and critical (n = 31)] and 14 healthy individuals were tested for a panel of 27 cytokines and chemokines using Luminex assay (27 Bio‑Plex Pro Human Cytokine, Bio-rad™).ResultsIL-12, IL-2 and IL-13, as well as IL-17 and GM-CSF were clearly undetectable in asymptomatic patients. IL-8 levels were higher in asymptomatic compared with other groups. Very high levels of IL-6, IL-10 and the chemokines MIP-1α, MCP-1 and IP10 were associated with disease progression, while IL-4 tends to decrease with disease severity.ConclusionOur study provides more evidence that excessive cytokine synthesis is linked to the disease progression.

The present study aims to screen some pharmacological activities of three promising ethacrynic acid (EA) derivatives (P3, P4, and P5) containing a piperazine moiety. The EA derivatives were tested against MDA-MB-468 cancer cell line as a model for the triple-negative breast cancer and MCF7 cancer cell line as a model subtype of luminal breast cancer using the methyl tetrazolium test (MTT). Additionally, the modulation of the glutathione and thioredoxin enzymatic systems, as well as the antioxidant and cytoprotective potential of each compound, were investigated. Moreover, initial in vitro safety screening was conducted using human blood cells. As a result, EA derivatives showed clear dose-dependent antiproliferative activity in the micromolar range (between 1.13 and 2.51 mu M), with high selectivity to cancer cells by orchestrating oxidative stress. Derivative P3 has the most promising potential for further preclinical investigation, owing to its safety profile and significant cytoprotective and antitumor properties.

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.

This chapter discusses the different types of genitourinary cancers and their close link with the immune system. It also elaborates on the immune biomarkers and the new immunotherapy options related to each genitourinary cancer type.

Women's breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)/MCF-7 and triple-negative breast cancer (TNBC)/MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 μM <IC50< 6 μM) with low cytotoxicity on normal cells (PBMC; IC50 ≥ 50 μM). Interestingly, these compounds were responsible for a substantial decrease in the clonogenic capacity of both cell lines. Moreover, dioscin was able to reduce the cell motility of the invasive breast cancer cells (MDA-MB-468). At the molecular level, the two treatments resulted in an increase of reactive oxygen species. Notably, both compounds were responsible for decreasing the enzymatic activities of glutathione reductase and thioredoxin reductase. On the basis of such considerations, protodioscin and dioscin may serve as promising natural compounds to treat TNBC and ER-positive breast cancer through the induction of oxidative stress.

The synthesis of a new family of seven new coordination complexes, with remarkable cytotoxicity and high selectivity index towards cancer cells when compared to peripheral blood mononuclear cells (PBMCs) is reported.

Hemi-synthesis, a process widely used in pharmacological research, consists of a modification in the chemical structure of a natural product in order to improve its activity and/or to reduce its side effects. Two carvacrol-derivatives (P1 and P2) have been synthetized using reactions of alkylation by binding alkan groups at the hydroxyl group of carvacrol. NMR analysis was performed for synthetized derivatives to confirm the success of the reactions. Then, cytotoxic activity, against two tumour cell lines (P-815 and MCF-7), and antibacterial activity of carvacrol, P1 and P2 were performed. Cytotoxicity was measured using the colourimetric methyl tetrazolium test (MTT) and antimicrobial activity was measured using the diffusion technique on solid media and the determination of CMI on liquid media. Our results show that chemical modifications made on carvacrol have no effect on its antitumor activity. However, an important decrease of its antibacterial activity was observed, especially for P1. Our results suggest that hydroxyl group at this position of the molecule may be responsible for carvacrol antibacterial activity, while the other parts of the molecule may be responsible for its antitumor activity. On the other hand, introduced modifications may affect mechanism of action of the molecules as well as its pharmacokinetics properties.

This work focused on the leaves of Dittrichia viscosa, a plant used in Mediterranean folk medicine. Compared to water extract, the methanolic extract had higher antioxidant effects. Moreover, this extract showed potent in vitro inhibitory activity against α-amylase and α-glucosidase and showed an interesting antiglycation effect. Additionally, the evaluation of the cytotoxic activity of the methanolic extract against two human breast cancer cell lines, MCF-7 and MDA-MB-468, was very promising, with no cytotoxicity towards normal cells (peripheral blood mononuclear cells (PBMCs). The antibacterial effect was also assessed and showed potent inhibitory activity against Proteus mirabilis and Bacillus subtilis. On the other hand, Dittrichia viscosa leaves were rich in macro-elements containing appropriate micro-elements and high levels of phenolics and flavonoids such as caffeic acid derivatives. Taken together, the results obtained in this study indicate that Dittrichia viscosa could constitute a valuable source of bioactive molecules and could be used either on the preventive side or for therapeutic applications without toxicity.

Advanced glycation end products (AGEs) generated from glycation might cause diseases such as diabetes and breast cancer. Antioxidants have an important role in protecting humans against infections and degenerative diseases due to their ability to neutralize AGEs. Olea europaea var. oleaster (Oeo) is an ancient plant widespread in the Mediterranean basin which is traditionally used as a source of antioxidants. The present research deals with phytochemical screening and the antioxidant properties of both aqueous and methanolic extracts of the Oeo fruit. Additionally, antidiabetic potential (α-amylase and α-glucosidase inhibitory activities) and inhibitory potential on AGEs formation have been investigated using the methanolic extract of the Oeo (ME-Oeo) fruit. The cytotoxic effect against two human breast cancer cell lines (MDA-MB-468 and MCF-7) was also investigated. Both aqueous and methanolic extracts showed a high phenolic and flavonoid content: by using HPLC-DAD-ESI/MS up to fifteen major compounds were positively identified. The methanolic extract showed better antioxidant activity than aqueous extract in all tests. Also, the ME-Oeo fruit showed high inhibitory effects on the production of Amadori products and AGEs from albumin in the presence of fructose and a high significant inhibitory effect against α-amylase (IC50 = 2.367 mg/mL) and α-glucosidase (IC50 = 1.272 mg/mL), respectively. The ME-Oeo fruit showed moderate cytotoxic activity against MDA-MB-468 cell line (IC50 = 35.16 µg/mL), and MCF-7 cell line (IC50 = 46.75 µg/mL). These results suggest the possibility of using ME-Oeo fruit as a source of natural bioactive compounds for the prevention of glycation-associated complications in diabetes and in cytotoxicity treatment.