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"Mnif, Wissem"
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The metabolism of cells regulates their sensitivity to NK cells depending on p53 status
2022
Leukemic cells proliferate faster than non-transformed counterparts. This requires them to change their metabolism to adapt to their high growth. This change can stress cells and facilitate recognition by immune cells such as cytotoxic lymphocytes, which express the activating receptor Natural Killer G2-D (NKG2D). The tumor suppressor gene p53 regulates cell metabolism, but its role in the expression of metabolism-induced ligands, and subsequent recognition by cytotoxic lymphocytes, is unknown. We show here that dichloroacetate (DCA), which induces oxidative phosphorylation (OXPHOS) in tumor cells, induces the expression of such ligands, e.g. MICA/B, ULBP1 and ICAM-I, by a wtp53-dependent mechanism. Mutant or null p53 have the opposite effect. Conversely, DCA sensitizes only wtp53-expressing cells to cytotoxic lymphocytes, i.e. cytotoxic T lymphocytes and NK cells. In xenograft in vivo models, DCA slows down the growth of tumors with low proliferation. Treatment with DCA, monoclonal antibodies and NK cells also decreased tumors with high proliferation. Treatment of patients with DCA, or a biosimilar drug, could be a clinical option to increase the effectiveness of CAR T cell or allogeneic NK cell therapies.
Journal Article
Unmasking the Fungicidal Potency and Multifaceted Mechanisms of Nutmeg Essential Oil Against Candida auris
by
Aljameel, Suhailah S.
,
Fatima, Zeeshan
,
Alghamdi, Zainab S.
in
Antifungal agents
,
Antimicrobial agents
,
biofilm
2026
Background: Candida auris has emerged as a multidrug-resistant fungal pathogen, presenting significant clinical challenges worldwide. Although considerable progress has been made in antifungal research, the specific mechanisms underlying drug resistance in C. auris remain incompletely understood. To overcome this problem, natural compounds can be used as valuable alternatives. The present study aimed to evaluate the antifungal activity of NEO against C. auris and to understand the functional mechanisms underlying its antifungal activity. Methods: The antifungal activity of NEO against C. auris strain CBS10913T was examined using broth microdilution and spot assays to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Mechanistic investigations were performed using phenotypic-, biochemical-, and fluorescence-based assays to evaluate its effects on cell wall integrity, membrane permeability, efflux pump activity, oxidative stress, lipid peroxidation, biofilm formation, and host cell adherence. Hemolytic assays were performed to evaluate preliminary biocompatibility. Results: During our study, we found that NEO showed strong fungicidal activity against C. auris, with an MIC of 500 µg/mL and an MFC of 650 µg/mL, and disrupted fungal cell wall integrity, significantly reduced ergosterol content, and inhibited efflux pump activity, leading to increased accumulation of fluorescent substrates. NEO induced increased intracellular reactive oxygen species, leading to oxidative-mediated lipid peroxidation and DNA damage. Moreover, NEO also suppressed stress biofilm formation, reduced metabolic activity, and decreased adherence to buccal epithelial cells, and it showed negligible hemolytic activity up to 2× MIC, indicating preliminary biocompatibility. Conclusions: This study demonstrates that NEO utilizes broad antifungal activity through multiple functional and phenotypic mechanisms, including disruption of membrane integrity, inhibition of efflux pump, induction of oxidative stress, and suppression of biofilm formation. Although the direct effects on pathogenicity-related genes or proteins were not studied, the findings still show NEO as a promising natural antifungal agent.
Journal Article
Bioflocculants as Alternative to Synthetic Polymers to Enhance Wastewater Sludge Dewaterability: A Review
2023
The dewatering process reduces the water quantity in sludge, allowing the decrease in its volume, which facilitates its storage, transport, stabilization, and improves the post-treatment efficiency. Chemical polymers including aluminum sulphate and polyaluminum chloride were applied as flocculants in the conditioning process in order to prepare sludge for dewatering. However, these synthetic polymers may cause risks for human health, and should be substituted with ecofriendly and safe materials. These materials include plant-based flocculants, animal-based flocculants, and microbial-based flocculants. Sludge dewaterability was evaluated by considering many parameters, such as moisture content (MC), dry solids (DS), specific resistance to filtration (SRF), capillary suction time (CST), and sludge volume index (SVI). The use of microorganisms for sludge dewatering is an available option, since many strains (R. erythropolis, A. ferrooxidans, P. mirabilis, T. flavus, etc.) demonstrated their ability to produce polymers useful for dewatering sludge from various origins (chemically treated primary sludge, activated sludge, anaerobically digested sludge, etc.). For plant-based flocculants, only okra (Abelmoschus esculentus), cactus (Opuntia ficus Indica), moringa (M. oleifera), and aloe (A. vera) plants are examined for sludge dewatering. Compared to synthetic polymers, plant-based flocculants showed a viable alternative to chemicals and a step forward in green sludge treatment technology. Among the animal-based flocculants, chitosan and aminated chitosan were able to reduce the SRF (SRF reduction rate > 80%) of the anaerobically digested sludge. A new strategy using methylated hemoglobin also showed a significant enhancement in cake solid content of sludge (47%) and a decrease in sludge bound water content of 17.30%. Generally, extensive investigations are needed to explore and optimize all the related parameters (operating conditions, preparation procedure, production cost, etc.) and to choose the appropriate materials for large-scale application.
Journal Article
Microbial Extracellular Polymeric Substances as Corrosion Inhibitors: A Review
2025
Microbial extracellular polymeric substances (EPSs) are emerging as sustainable alternatives to conventional corrosion inhibitors due to their eco-friendly nature, biodegradability, and functional versatility. Secreted by diverse microorganisms including bacteria, fungi, archaea, and algae, EPSs are composed mainly of polysaccharides, proteins, lipids, and nucleic acids. These biopolymers, chiefly polysaccharides and proteins, are accountable for surface corrosion prevention through biofilm formation, allowing microbial survival and promoting their environmental adaptation. Usually, EPS-mediated corrosion inhibitions can take place via different mechanisms: protective film formation, metal ions chelation, electrochemical property alteration, and synergy with inorganic inhibitors. Even though efficacious EPS corrosion prevention has been demonstrated in several former studies, the application of such microbial inhibitors remains, so far, a controversial topic due to the variability in their composition and compatibility toward diverse metal surfaces. Thus, this review outlines the microbial origins, biochemical properties, and inhibition mechanisms of EPSs, emphasizing their advantages and challenges in industrial applications. Advances in synthetic biology, nanotechnology, and machine learning are also highlighted and could provide new opportunities to enhance EPS production and functionality. Therefore, the adoption of EPS-based corrosion inhibitors represents a promising strategy for environmentally sustainable corrosion control.
Journal Article
A Brief Review on New Naturally Occurring Cembranoid Diterpene Derivatives from the Soft Corals of the Genera Sarcophyton, Sinularia, and Lobophytum Since 2016
by
Rodrigues, Inna Glibka
,
Mnif, Wissem
,
Miguel, Maria Graça
in
anti-inflammatory
,
anti-microbial
,
anti-tumoral
2019
This work reviews the new isolated cembranoid derivatives from species of the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2018. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton than in those belonging to the genera Lobophytum or Sinularia. Beyond the chemical composition, the biological properties were also reviewed, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. In spite of the biological activities detected in almost all samples, there is a remarkable diversity in the results which may be attributed to the chemical variability that needs to be deepened in order to develop new molecules with potential application in medicine.
Journal Article
Effect of Endocrine Disruptor Pesticides: A Review
by
Roig, Benoit
,
Mnif, Wissem
,
Hassine, Aziza Ibn Hadj
in
Endocrine disruptors
,
Endocrine Disruptors - toxicity
,
Endocrine system
2011
Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.
Journal Article
Effective Heavy Metals Removal from Water Using Nanomaterials: A Review
by
Ben Rebah, Faouzi
,
Mnif, Wissem
,
Siddeeg, Saifeldin M.
in
Chemical properties
,
Heavy metals
,
Identification and classification
2020
The discharge of toxic heavy metals including zinc (Zn), nickel (Ni), lead (Pb), copper (Cu), chromium (Cr), and cadmium (Cd) in water above the permissible limits causes high threat to the surrounding environment. Because of their toxicity, heavy metals greatly affect the human health and the environment. Recently, better remediation techniques were offered using the nanotechnology and nanomaterials. The attentions were directed toward cost-effective and new fabricated nanomaterials for the application in water/wastewater remediation, such as zeolite, carbonaceous, polymer based, chitosan, ferrite, magnetic, metal oxide, bimetallic, metallic, etc. This review focused on the synthesis and capacity of various nanoadsorbent materials for the elimination of different toxic ions, with discussion of the effect of their functionalization on the adsorption capacity and separation process. Additionally, the effect of various experimental physicochemical factors on heavy metals adsorption, such as ionic strength, initial ion concentration, temperature, contact time, adsorbent dose, and pH was discussed.
Journal Article
Optimization of Protease and Amylase Production by Rhizopus oryzae Cultivated on Bread Waste Using Solid-State Fermentation
by
M’Hir, Sana
,
Mnif, Wissem
,
Benabda, Olfa
in
Agricultural biotechnology
,
Aluminum
,
Ammonium chloride
2019
This research was carried for the coproduction of two industrial enzymes: α-amylase and protease via SSF by Rhizopus oryzae on humidified bread waste. Fermentation time, inoculum size, initial moisture content, salt solutions, and the thickness of the substrate were investigated one by one. Fungus culture was carried out in sterile aluminum trays, and pH was adjusted to 5.5. The main results showed that the highest levels of enzyme production were obtained at 120 h, 65% relative humidity, height media of 1 cm, 105 spore/g, and M-9 solution (g/L): NaH2PO4, 12.8; KH2PO4, 3; NaCl, 0.5; NH4Cl, 1; MgSO4 7H2O, 0.5; CaCl2 2H2O, 0.01. α-Amylase (100 U/g) and protease (2400 U/g) produced by SSF from Rhizopus oryzae (CH4) on BW as substrate are of great interest in industries and could be valorized as enhancers of the bread making process.
Journal Article
Microbial Flocculants as an Alternative to Synthetic Polymers for Wastewater Treatment: A Review
2018
Microorganisms such as bacteria, fungi, and microalgae have been used to produce bioflocculants with various structures. These polymers are active substances that are biodegradable, environmentally harmless, and have flocculation characteristics. Most of the developed microbial bioflocculants displayed significant flocculating activity (FA > 70–90%) depending on the strain used and on the operating parameters. These biopolymers have been investigated and successfully used for wastewater depollution in the laboratory. In various cases, selected efficient microbial flocculants could reduce significantly suspended solids (SS), turbidity, chemical oxygen demand (COD), total nitrogen (Nt), dye, and heavy metals, with removal percentages exceeding 90% depending on the bioflocculating materials and on the wastewater characteristics. Moreover, bioflocculants showed acceptable results for sludge conditioning (accepted levels of dry solids, specific resistance to filtration, moisture, etc.) compared to chemicals. This paper explores various bioflocculants produced by numerous microbial strains. Their production procedures and flocculating performance will be included. Furthermore, their efficiency in the depollution of wastewater will be discussed.
Journal Article
The Chemical Variability, Nutraceutical Value, and Food-Industry and Cosmetic Applications of Citrus Plants: A Critical Review
by
Morais, Simone
,
Sadaka, Carmen
,
Ben Hsouna, Anis
in
Bioactive compounds
,
By products
,
Carotenoids
2023
Citrus fruits occupy an important position in the context of the fruit trade, considering that both fresh fruits and processed products are produced on a large scale. Citrus fruits are recognized as an essential component of the human diet, thanks to their high content of beneficial nutrients such as vitamins, minerals, terpenes, flavonoids, coumarins and dietary fibers. Among these, a wide range of positive biological activities are attributed to terpenes and flavonoids derivatives. In this review, a list of bibliographic reports (from 2015 onwards) on the phytochemical composition, beneficial effects and potential applications of citrus fruits and their by-products is systematically summarized. In detail, information regarding the nutraceutical and medicinal value closely linked to the presence of numerous bioactive metabolites and their growing use in the food industry and food packaging, also considering any technological strategies such as encapsulation to guarantee their stability over time, were evaluated. In addition, since citrus fruit, as well as its by-products, are interesting alternatives for the reformulation of natural cosmetic products, the sector of the cosmetic industry is also explored. More in-depth knowledge of the latest information in this field will contribute to future conscious use of citrus fruits.
Journal Article