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Background. Health and social management of the SARS-CoV-2 epidemic, responsible for the COVID-19 disease, requires both screening tools and diagnostic procedures. Reliable screening tests aim at identifying (truely) infectious... more
Background. Health and social management of the SARS-CoV-2 epidemic, responsible for the COVID-19 disease, requires both screening tools and diagnostic procedures. Reliable screening tests aim at identifying (truely) infectious individuals that can spread the viral infection and therefore are essential for tracing and harnessing the epidemic diffusion. Instead, diagnostic tests should supplement clinical and radiological findings, thus helping in establishing the diagnosis. Several analytical assays, mostly using RT-PCR-based technologies, have become commercially available for healthcare workers and clinical laboratories. However, such tests showed some critical limitations, given that a relevant number of both false-positive and false-negative cases have been so far reported. Moreover, those analytical techniques demonstrated to be significantly influenced by pre-analytical biases, while the sensitivity showed a dramatic time dependency. Aim. Herein, we critically investigate limi...
In this review, we explore the current literature on the influence of the plant isoflavone daidzein and its metabolite equol on animal and human physiological processes, with an emphasis on female reproduction including ovarian functions... more
In this review, we explore the current literature on the influence of the plant isoflavone daidzein and its metabolite equol on animal and human physiological processes, with an emphasis on female reproduction including ovarian functions (the ovarian cycle; follicullo- and oogenesis), fundamental ovarian-cell functions (viability, proliferation, and apoptosis), the pituitary and ovarian endocrine regulators of these functions, and the possible intracellular mechanisms of daidzein action. Furthermore, we discuss the applicability of daidzein for the control of animal and human female reproductive processes, and how to make this application more efficient. The existing literature demonstrates the influence of daidzein and its metabolite equol on various nonreproductive and reproductive processes and their disorders. Daidzein and equol can both up- and downregulate the ovarian reception of gonadotropins, healthy and cancerous ovarian-cell proliferation, apoptosis, viability, ovarian gr...
The agenda of pharmacology discovery in the field of personalized oncology was dictated by the search of molecular targets assumed to deterministically drive tumor development. In this perspective, genes play a fundamental “causal” role... more
The agenda of pharmacology discovery in the field of personalized oncology was dictated by the search of molecular targets assumed to deterministically drive tumor development. In this perspective, genes play a fundamental “causal” role while cells simply act as causal proxies, i.e., an intermediate between the molecular input and the organismal output. However, the ceaseless genomic change occurring across time within the same primary and metastatic tumor has broken the hope of a personalized treatment based only upon genomic fingerprint. Indeed, current models are unable in capturing the unfathomable complexity behind the outbreak of a disease, as they discard the contribution of non-genetic factors, environment constraints, and the interplay among different tiers of organization. Herein, we posit that a comprehensive personalized model should view at the disease as a “historical” process, in which different spatially and timely distributed factors interact with each other across ...
Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates... more
Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell death during weightlessness. These controversial results can be explained by considering the notion that the behavior of adherent cells dramatically diverges in respect to that of detached cells, organized into organoids-like, floating structures. We investigated both normal (MCF10A) and cancerous (MCF-7) breast cells and found that appreciable apoptosis occurs only after 72 h in MCF-7 cells growing in organoid-like structures, in which major modifications of cytoskeleton components were observed. Indeed, preserving cell attachment to the substrate allows cells to upregulate distinct Akt- and ERK-dependent pathways in MCF-7 and MCF-10A cel...
Abstract Background The influence of plant isoflavone rutin (vitamin P) on healthy ovarian cells is unknown. Methods We evaluated the effect of FSH alone, at various dose levels (0, 10, 100, or 1000 ng/mL), and in combination with rutin... more
Abstract Background The influence of plant isoflavone rutin (vitamin P) on healthy ovarian cells is unknown. Methods We evaluated the effect of FSH alone, at various dose levels (0, 10, 100, or 1000 ng/mL), and in combination with rutin (10 μg/mL) on the markers of viability (trypan blue test), proliferation (expression of proliferating cell nuclear antigen, PCNA and cyclin B1), apoptosis (expression of Bcl-2-associated X protein, bax and caspase 3) (by quantitative immunocytochemistry), and release of progesterone (P), testosterone (T), and estradiol (E) (by ELISA) in cultured porcine ovarian granulosa cells. Results FSH increased cell viability, proliferation, and release of steroid hormones; FSH inhibited apoptosis. When added alone, rutin decreased cell viability, proliferation and apoptosis and promoted P, T and E output. Furthermore, when added together with FSH, it suppressed all the FSH effects. Conclusion The present observations demonstrate the ability of rutin to directly promote ovarian cell steroidogenesis and to suppress their viability, proliferation, apoptosis, and response to the stimulatory action of FSH. Such adverse effects of rutin on ovarian cells should be taken into account regarding consumption of food and use of medical preparations containing rutin and its metabolites.
We sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at... more
We sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at pre-pubertal age (week 4) and during adulthood (week 8). At week 4, MFR significantly increased the expression of RNAs for all analyzed genes in both FRG1 and FRG2 females, which may indicate that MFR affects the onset of the reproductive lifespan, by inducing early pubertal onset. At week 8, the Cyp19 gene was still upregulated in MRF-subjected animals (Cyp19: P=0.0049 and P=0.0508 in FRG1 and FRG2, respectively), but MFR induced a significant decrease in Cyp17 and Gdf-9 gene expression in the offspring of both FRG1 and FRG2 females when compared with the controls (Cyp17: P=0.0018 and P=0.0016, respectively; Gdf-9: P=0.0047 and P=0.0023, respectively). This suggests that females at week 8, which should normally be in their optimal reproductive capaci...
Two new monoterpene Ducrosin A (1) and sesquiterpene Ducrosin B (2) were isolated along with three known compounds, stigmasterol (3) and two furanocoumarins (4 and 5), from the dichloromethane extract of the seeds of Ducrosia anethifolia... more
Two new monoterpene Ducrosin A (1) and sesquiterpene Ducrosin B (2) were isolated along with three known compounds, stigmasterol (3) and two furanocoumarins (4 and 5), from the dichloromethane extract of the seeds of Ducrosia anethifolia (DC.) Boiss. Their structures were determined using extensive 1D and 2D NMR, (ES)-HRMS and IR spectroscopic analyses and by comparison with literature data. Gas chromatography analysis of the fatty acids (FAs) of D. anethifolia seed oils (DAOs) showed high percentages of elaidic acid (C18:1 Δ9t) 65% and oleic acid (C18:1 Δ9c) 15%. The total tocopherol (tocols) content in DAOs was found to be 164 mg/100 g. The cytotoxic effect of the isolates was also evaluated using the MTT assay against the HCT-116 and SKOV-3 cell lines. The results showed that compound 2 was the most cytotoxic agent followed by compounds 1 and 4, which has an epoxide moiety that most likely contributes to its activity.
Benign mammary lumps and mastalgia are the most common breast disorders; yet, there is no clear-cut consensus about the best strategy for their treatment. We hypothesized that a combination, including boswellic acid, betaine, and... more
Benign mammary lumps and mastalgia are the most common breast disorders; yet, there is no clear-cut consensus about the best strategy for their treatment. We hypothesized that a combination, including boswellic acid, betaine, and myoinositol, would be beneficial in breast disorders by exerting a pleiotropic effect on multiple pathways. Indeed, myoinositol has already been proven to modulate some factors involved in the genesis of breast diseases, such as fibrosis and metabolic and endocrine cues. In our study, 76 women were randomly assigned to either the experimental or the placebo arm. After six months of treatment, statistically significant differences between the two groups were recorded for pain relief (56% vs 17%) and breast density reduction (60% vs 9%). Furthermore, benign breast mass dimension showed a reduction in the experimental group (40% vs 16%). The combination of boswellic acid, betaine, and myoinositol has been demonstrated to be effective in the treatment of breast...
This study was carried out to investigate a paradigm of predation under natural conditions in Bizerta lagoon. The free-living marine polyclad flatworm Imogine mediterranea was found to feed on the commercial mussel Mytilus... more
This study was carried out to investigate a paradigm of predation under natural conditions in Bizerta lagoon. The free-living marine polyclad flatworm Imogine mediterranea was found to feed on the commercial mussel Mytilus galloprovincialis. Such predation could represent a real threat to mytiliculture at this site. Our field experiments have shown that the mortality of the commercial mussel as a result of active predation by this polyclad is approximately 52% when one polyclad and one prey were placed together in a same experimental container. We found a statistically significant relationship between the size of the polyclad and the extent to which the mussels were disabled or completely eaten. Moreover, in our field experiments, the times required for predation-caused decreases of populations of the bivalves, that is, LT10, LT25 and LT50, decreased significantly with increases in the size of the polyclad. The time, LT50, required for polyclads to kill half of the bivalve population in field experiments was approximately 4.5 days. A simple disabling (an attack by the polyclad on the adductor muscle of the mussel) was shown to be sufficient to cause irreversible changes leading to mortality. Furthermore, disabling and mortality were found to be linearly correlated. The importance of mucous secretions, pharyngeal type and body musculature in supporting predation by polyclads is discussed. We suggest that measures to control the polyclad pest could incorporate the control of this flatworm's embryonic and postembryonic developmental stages.
The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of... more
The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our ...
Abstract The ecology of Schmidtea mediterranea, a freshwater planarian, is here described for the first time from Tunisia. The population consists of sexual diploids with a chromosome number of 2n= 8, and reproduces exclusively sexually... more
Abstract The ecology of Schmidtea mediterranea, a freshwater planarian, is here described for the first time from Tunisia. The population consists of sexual diploids with a chromosome number of 2n= 8, and reproduces exclusively sexually through the formation of cocoons. ...
<i> Ceratomyxa pallida Thélohan</i> ı<i> 1894</i> (<i> Figure 2</i>)<i> Myxospore morphology</i> The mature myxospores typical of the genus<i> Ceratomyxa</i> were... more
<i> Ceratomyxa pallida Thélohan</i> ı<i> 1894</i> (<i> Figure 2</i>)<i> Myxospore morphology</i> The mature myxospores typical of the genus<i> Ceratomyxa</i> were crescent-shaped. The anterior margin was archedı and the posterior margin was concave. Valves were equal with rounded and tapered ends. A slightly curved sutural line was visible between the two valves. The sporoplasm filled half of the myxospore cavity. The myxospores measured 6 ± 0.5 (5<i> –</i> 7) µm in length and 28.5 ± 2.5 (26<i> –</i> 33) µm in thickness. The polar capsules were sphericalı equal in size and measured 3 ± 0.3 (2.7<i> –</i> 3.3) in diameter. Polar filaments in the capsule were not discernible.<i> Vegetative stage</i> Spherical to elongated monosporousı disporous and trisporous plasmodia were found floating in the bile. The measurements of the plasmodia were 29 ± 5.3 × 10 ± 2.5 µm. A schematic drawing of the myxospore and plasmodiaı based on light microscope observationsı is shown in Figure 2.[table omitted]<i> SSU rDNA sequence</i> A consensus sequence of 1547 bp of the SSU rDNA was generated from three different sequenced samples and was submitted under accession number FJ710895. Two sequences from the six sequenced clones were identical to the sequences obtained from samples individually infected by<i> C. pallida</i>. The sequence of<i> C. pallida</i> has 97.5% of similarity with<i> C. ghannouchensis</i> ı and 94.4% with<i> C. tunisiensis</i> Thabetı Mansourı Al Omar and Tlig-Zouariı 2015.<i> Taxonomic summary</i><i> Location in the host</i>. Coelozoicı in the bile<i> Type host</i>. Bogueı<i> Boops boops</i> (Linnaeus) ( Perciformes: Sparidae)<i> site of infection</i>. Lumen and wall of the gallbladder.<i> Prevalence</i>. Sixty-three per cent (99 out of 157 examined specimens).<i> Type location</i>. Ghannouch in the Gulf of Gabèsı (33°56<i> ′</i> 37.6<i> ″</i> Nı 10°04<i> ʹ</i> 42.7<i> ″</i> E)ı south of Tunisia.<i> Deposited</i>. Photosyntype (ZS141)ı one air-dried slide stained with Giemsa (ZS142) and myxospores in absolute ethan [...]
Figure 4. Phylogenetic tree of Ceratomyxa spp. resulting from maximum likelihood analysis using the SSU rDNA dataset showing the position of Ceratomyxa ghannouchensis n. sp. and Ceratomyxa pallida. Support values based on 1000 replicates... more
Figure 4. Phylogenetic tree of Ceratomyxa spp. resulting from maximum likelihood analysis using the SSU rDNA dataset showing the position of Ceratomyxa ghannouchensis n. sp. and Ceratomyxa pallida. Support values based on 1000 replicates are indicated at branching nodes listed as bootstrap values from maximum likelihood/Bayesian posterior probabilities from Bayesian analysis. Tetracapsuloides bryosalmonae was used as outgroup. Values below 70% or not supported by the analysis are indicated by dashes. Scale bar is probability of nucleotide change.
Figure 1. Ceratomyxa ghannouchensis n. sp. from the gall bladder of Boops boops. (a) Fresh myxospore; (b) monosporous plasmodia; (c) line drawing of the mature myxospore. Scale bars = 5 µm.
Ethylbenzene is a hydrocarbon that is extensively used in both industry and in the home and has been reported as toxic to various tissues. Nevertheless, its effect on ovarian function remains unclear. For this purpose, we assessed ovarian... more
Ethylbenzene is a hydrocarbon that is extensively used in both industry and in the home and has been reported as toxic to various tissues. Nevertheless, its effect on ovarian function remains unclear. For this purpose, we assessed ovarian tissue morphology, evaluated protein and gene expression related to folliculogenesis and steroidogenesis, and investigated the involvement of both apoptosis and autophagy processes in this effect. Female Wistar albinos rats were treated with 2000, 4000 and 8000 ppm doses of ethylbenzene by inhalation for 30 min daily for one month. Ovaries were then removed and proceeded for histopathological and molecular analyses. We found that ethylbenzene affected folliculogenesis by decreasing the number of growing follicles and increasing the number of abnormal follicles, leading to faster female reproductive aging. Interestingly, it disrupted female reproductive hormone balance, including progesterone, estradiol, testosterone and IGF-1 plasma levels. The latter protein, along with GDF-9, significantly decreased in all ethylbenzene-treated groups, leading to the disruption of follicular cell proliferation and development. TUNEL assay study showed that ethylbenzene exposure significantly increased the number of apoptotic cells. The mRNA levels of genes involved in granulosa cell proliferation and differentiation, such as INSL3, CCND2 and ACTB, were significantly decreased. In addition, LC3 protein expression increased, and its encoding gene was upregulated, suggesting that ethylbenzene treatment induced autophagy. In summary, ethylbenzene exposure caused structural and functional disorders of the ovary by disrupting the normal growth of follicles, altering reproductive hormone balance, inhibiting the expression of key reproductive proteins and triggering autophagy as well as apoptosis.
The toxicity of copper, cadmium, and dieldrin in adult Gammarus locusta (a marine amphipod) is currently unclear. Thus, G. locusta from the North Lake of Tunis were subjected to acute toxicity tests to assess LC50s at 48–96 h and to... more
The toxicity of copper, cadmium, and dieldrin in adult Gammarus locusta (a marine amphipod) is currently unclear. Thus, G. locusta from the North Lake of Tunis were subjected to acute toxicity tests to assess LC50s at 48–96 h and to biomarker response tests through the assessment of catalase and acetylcholinesterase activities and malondialdehyde levels. The present study demonstrated the abilities of a chlorinated hydrocarbon pesticide (dieldrin) induce to oxidative stress and neurotoxicity. The comparison of metal toxicity showed that G. locusta was more sensitive to cadmium than copper. The three stressors caused significant inductions of all three biomarkers in a concentration-dependent manner. Catalase induction was dependent on exposure duration for all pollutants, while only copper led to increased malondialdehyde with longer exposure times. Catalase induction and malondialdehyde increase appeared to be sex dependent for all three pollutants. The neurotoxic effects of the pollutants were concentration dependent according to inhibition of acetylcholinesterase activity. In conclusion, catalase, malondialdehyde, and acetylcholinesterase are efficient biomarkers of copper, cadmium, and dieldrin in G. locusta.
Numerous studies have focused on the response of meiofauna after exposure to polycyclic aromatic hydrocarbons (PAHs), but none has been devoted to their uptake into nematode body compartments. The present study monitored PAH uptake by... more
Numerous studies have focused on the response of meiofauna after exposure to polycyclic aromatic hydrocarbons (PAHs), but none has been devoted to their uptake into nematode body compartments. The present study monitored PAH uptake by Oncholaimus campylocercoides which was selected after 40 days in the laboratory through original protocols from natural sediments collected in the Old Harbor of Bizerte, Tunisia. To achieve the mono-species level, a grain size magnification was applied by gradually adding a biosubstrate made from either the crushed shells of Mytilus galloprovincialis or minced leaves of Posidonia oceanica. After selection, O. campylocercoides was cultured and fed with earthworm powder (560 mg.l-1). Thereafter, it was exposed for 3 weeks to phenanthrene and chrysene (38, 116, and 348 ppb). Fluorescence microscopy revealed higher intensities of PAHs at the spicules, mouths, and pharynges compared with the other organs considered. Moreover, the buccal fluorescence showed a significant correlation with that measured in the biosubstrate made with shells of M. galloprovincialis.
Andrographolide (ANDR), isolated from Andrographis paniculata, is a medicinal compound effective against infections, inflammatory disorders, and various cancers. In the present study, the effects of ANDR on NFkB (nuclear factor... more
Andrographolide (ANDR), isolated from Andrographis paniculata, is a medicinal compound effective against infections, inflammatory disorders, and various cancers. In the present study, the effects of ANDR on NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, caspase-8-mediated apoptosis and pyroptosis, and extra cellular matrix (ECM) degradation were analyzed in A431, MDA-MB231, and SKOV-3 cell lines. Results showed that ANDR inhibited the growth and proliferation of cancer cell lines by inhibiting NFkB signaling. A significant decrease in phospho-p65 level was observed upon increasing ANDR concentration in epidermoid carcinoma and breast cancer cell lines, A431 and MDA-MB231, respectively. Accordingly, upon ANDR treatment, the expression of caspase-8 was increased, whereas no significant induction of caspase-1 expression was observed. Moreover, we observed a significant increase in the expression of tissue inhibitor of metallopeptidase-1 (TIMP1) upon i...
A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl2(p-cymene)]2in dichloromethane under Ar... more
A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl2(p-cymene)]2in dichloromethane under Ar conditions.
The bioflavonoid quercetin is a component of food with numerous biological effects, but its function in reproductive processes remains to be investigated. This study aimed to examine the direct action of quercetin on steroid hormone... more
The bioflavonoid quercetin is a component of food with numerous biological effects, but its function in reproductive processes remains to be investigated. This study aimed to examine the direct action of quercetin on steroid hormone release in rabbit ovaries. We analysed the effect of quercetin (0, 1, 10, and 100 ng/mL) on cultured rabbit ovarian fragments. The release of progesterone (P4), testosterone (T) and estradiol (E2) were analysed by enzyme immunoassay. Quercetin promoted P4, T, and E2 release by rabbit ovarian fragments. These observations indicate that quercetin can directly stimulate rabbit ovarian steroidogenesis – an essential regulator of reproduction and fecundity. The application of dietary quercetin for control of rabbit reproduction is discussed.
Invasions of alien species form one of the major threats to global biodiversity. Among planarian flatworms many species are known to be invasive, in several cases strongly affecting local ecosystems. Therefore, a detailed knowledge on the... more
Invasions of alien species form one of the major threats to global biodiversity. Among planarian flatworms many species are known to be invasive, in several cases strongly affecting local ecosystems. Therefore, a detailed knowledge on the biology of an invasive species is of utmost importance for understanding the process of invasion, the cause of its success, and the subsequent ecological impact on native species. This paper provides new information on the biology of introduced populations of the freshwater flatworm Girardia tigrina (Girard, 1850) from Europe. This species is a native of the Nearctic Region that was accidentally introduced into Europe in the 1920s. Since then, numerous records across the European continent bear witness of the invasiveness of this species, although only a few studies focused on the biology of the introduced populations. We report on the morphology of sexualized individuals from a fissiparous Italian population, representing the second record of spon...
Superparamagnetic Fe₃O₄ nanoparticles on hydroxyapatite nanorod based nanostructures (Fe₃O₄/HAp) were synthesized using hydrothermal techniques at 180 °C for 12 h and were used as drug delivery nanocarriers for cancer cell therapeutic... more
Superparamagnetic Fe₃O₄ nanoparticles on hydroxyapatite nanorod based nanostructures (Fe₃O₄/HAp) were synthesized using hydrothermal techniques at 180 °C for 12 h and were used as drug delivery nanocarriers for cancer cell therapeutic applications. The synthesized Fe₃O₄/HAp nanocomposites were characterized by X-ray diffraction analysis (XRD), Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET)-analysis, and vibrating sample magnetometry (VSM). The morphologies of the Fe₃O₄/HAp nanocomposites show 15 nm Fe₃O₄ nanoparticles dispersed in the form of rods. The BET result shows that the synthesized samples have a high specific surface area of 80 m² g(-1) with mesoporous structures. Magnetic measurements revealed that the sample has high saturation magnetization of 18 emu/g with low coercivity. The Fe₃O₄/HAp nanocomposites had a large specific surface area (SSA), high mesoporous volume, and good magnetic proper...

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