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Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD) to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.

Orobanche spp. are root parasitic plants that cause severe yield losses in faba bean ( Vicia faba L.). The use of tolerant varieties remains a pivotal component of a successful integrated control strategy. In this study, we investigated the potential physiological mechanisms associated with tolerance to O. crenata and O. foetida in faba bean. The results showed that Orobanche parasitism significantly affected faba bean plants' growth and seed production, especially in the sensitive Bachaar variety (up to 61.77% and 83.53% in shoot dry weight, up to 79.59% in pod number and no pod development when infected with O. foetida and O. crenata , respectively). This reduction was correlated with photosynthetic capacity (A max ) decreases in response to both O. foetida and O. crenata parasitism. This decrease was highly pronounced in the sensitive Bachaar variety with 24.57% and 63.43% decreases, respectively. Significant decreases were also observed in the sensitive Bachaar cultivar for the photochemical efficiency of PSII (F v /F m ) (1.1% and 4.78%), the maximum transpiration (E max ) (11.8% and 39.13%), and the maximum water use efficiency (WUE max ) (24.97% and 41.77%) in response to O. foetida and O. crenata parasitism, respectively, compared to non-significant differences for the tolerant Chams, Chourouk, and Zaher varieties. The tolerant faba bean varieties were able to maintain a normal function of their photosynthesis capacity (A n ) and conserve their growth and seed production level as a result of an acclimation to parasitic attack (Maintaining WUE max ). Our results suggest that yield components such as shoot dry weight, pod and leaf numbers, and photosynthetic parameters, notably the transpiration rate, can serve as suitable traits for assessing tolerance to Orobanche parasitism in faba bean plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thebti, Bouallegue, Rzigui, En-Nahli, Horchani, Hosni, Kharrat, Amri and Abbes.)

Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides including octadecaneuropeptide (ODN). We have previously reported that ODN rescues neurons and astrocytes from 6-OHDA-induced oxidative stress and cell death. The purpose of this study was to examine the potential implication of miR-34b, miR-29a, and miR-21 in the protective activity of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Flow cytometry analysis showed that 6-OHDA increased the number of early apoptotic and apoptotic dead cells while treatment with the subnanomolar dose of ODN significantly reduced the number of apoptotic cells induced by 6-OHDA. 6-OHDA-treated astrocytes exhibited the over-expression of miR-21 (+118%) associated with a knockdown of miR-34b (-61%) and miR-29a (-49%). Co-treatment of astrocytes with ODN blocked the 6-OHDA-stimulated production of ROS and NO and stimulation of Bax and caspase-3 gene transcription. Concomitantly, ODN down-regulated the expression of miR-34b and miR-29a and rescued the 6-OHDA-associated reduced expression of miR21, indicating that ODN regulates their expression during cell death. Transfection with miR-21-3p inhibitor prevented the effect of 6-OHDA against cell death. In conclusion, our study indicated that (i) the expression of miRNAs miR-34b, miR-29a, and miR-21 is modified in astrocytes under 6-OHDA injury and (ii) that ODN prevents this deregulation to induce its neuroprotective action. The present study identified miR-21 as an emerging candidate and as a promising pharmacological target that opens new neuroprotective therapeutic strategies in neurodegenerative diseases, especially in Parkinson's disease.

Background: Congenital scoliosis (CS) is a spinal disorder caused by genetic-congenital vertebral malformations and may be associated with other congenital defects or may occur alone. It is genetically heterogeneous and numerous genes contributing to this disease have been identified. In addition, CS has a wide range of phenotypic and genotypic variability, which has been explained by the intervention of genetic factors like modifiers and environment genes. The aim of the present study was to determine the possible cause of CS in a Tunisian patient and to examine the association between mtDNA mutations and mtDNA content and CS., Methods: Here we performed Whole-Exome Sequencing (WES) in a patient presenting clinical features suggestive of severe congenital scoliosis syndrome. Direct sequencing of the whole mitochondrial DNA (mtDNA) was also performed in addition to copy number quantification in the blood of the indexed case. In silico prediction tools, 3D modeling and molecular docking approaches were used., Results: The WES revealed the homozygous missense mutation c.512A > G (p.H171R) in the TBXT gene. Bioinformatic analysis demonstrated that the p.H171R variant was highly deleterious and caused the TBXT structure instability. Molecular docking revealed that the p.H171R mutation disrupted the monomer stability which seemed to be crucial for maintaining the stability of the homodimer and consequently to the destabilization of the homodimer-DNA complex. On the other hand, we hypothesized that mtDNA can be a modifier factor, so, the screening of the whole mtDNA showed a novel heteroplasmic m.10150T > A (p.M31K) variation in the MT-ND3 gene. Further, qPCR analyses of the patient's blood excluded mtDNA depletion. Bioinformatic investigation revealed that the p.M31K mutation in the ND3 protein was highly deleterious and may cause the ND3 protein structure destabilization and could disturb the interaction between complex I subunits., Conclusion: We described the possible role of mtDNA genetics on the pathogenesis of congenital scoliosis by hypothesizing that the presence of the homozygous variant in TBXT accounts for the CS phenotype in our patient and the MT-ND3 gene may act as a modifier gene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intellectual disabilities (ID) and autism spectrum disorders (ASD) have a variety of etiologies, including environmental and genetic factors. Our study reports a psychiatric clinical investigation and a molecular analysis using whole exome sequencing (WES) of two siblings with ID and ASD from a consanguineous family. Bioinformatic prediction and molecular docking analysis were also carried out. The two patients were diagnosed with profound intellectual disability, brain malformations such as cortical atrophy, acquired microcephaly, and autism level III. The neurological and neuropsychiatric examination revealed that P2 was more severely affected than P1, as he was unable to walk, presented with dysmorphic feature and exhibited self and hetero aggressive behaviors. The molecular investigations revealed a novel TRAPPC9 biallelic nonsense mutation (c.2920 C > T, p.R974X) in the two siblings. The more severely affected patient (P2) presented, along with the TRAPPC9 variant, a new missense mutation c.166 C > T (p.R56C) in the MID2 gene at hemizygous state, while his sister P1 was merely a carrier. The 3D modelling and molecular docking analysis revealed that c.166 C > T variant could affect the ability of MID2 binding to Astrin, leading to dysregulation of microtubule dynamics and causing morphological abnormalities in the brain. As our knowledge, the MID2 mutation (p.R56C) is the first one to be detected in Tunisia and causing phenotypic variability between the siblings. We extend the genetic and clinical spectrum of TRAPPC9 and MID2 mutations and highlights the possible concomitant presence of X-linked as well as autosomal recessive inheritance to causing ID, microcephaly, and autism., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Plant growth-promoting rhizobacteria (PGPR) applications have emerged as an ideal substitute for synthetic chemicals by their ability to improve plant nutrition and resistance against pathogens. In this study, we isolated fourteen root endophytes from healthy wheat roots cultivated in Tunisia. The isolates were identified based from their 16S rRNA gene sequences. They belonged to Bacillota and Pseudomonadota taxa. Fourteen strains were tested for their growth-promoting and defense-eliciting potentials on durum wheat under greenhouse conditions, and for their in vitro biocontrol power against Fusarium culmorum, an ascomycete responsible for seedling blight, foot and root rot, and head blight diseases of wheat. We found that all the strains improved shoot and/or root biomass accumulation, with Bacillus mojavensis, Paenibacillus peoriae and Variovorax paradoxus showing the strongest promoting effects. These physiological effects were correlated with the plant growth-promoting traits of the bacterial endophytes, which produced indole-related compounds, ammonia, and hydrogen cyanide (HCN), and solubilized phosphate and zinc. Likewise, plant defense accumulations were modulated lastingly and systematically in roots and leaves by all the strains. Testing in vitro antagonism against F. culmorum revealed an inhibition activity exceeding 40% for five strains: Bacillus cereus, Paenibacillus peoriae, Paenibacillus polymyxa, Pantoae agglomerans, and Pseudomonas aeruginosa. These strains exhibited significant inhibitory effects on F. culmorum mycelia growth, sporulation, and/or macroconidia germination. P. peoriae performed best, with total inhibition of sporulation and macroconidia germination. These finding highlight the effectiveness of root bacterial endophytes in promoting plant growth and resistance, and in controlling phytopathogens such as F. culmorum. This is the first report identifying 14 bacterial candidates as potential agents for the control of F. culmorum, of which Paenibacillus peoriae and/or its intracellular metabolites have potential for development as biopesticides., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saadaoui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Orobanche foetida Poiret is the main constraint facing faba bean crop in Tunisia. Indeed, in heavily infested fields with this parasitic plant, yield losses may reach 90%, and the recent estimation of the infested area is around 80,000 ha. Identifying genes involved in the Vicia faba/O. foetida interaction is crucial for the development of effective faba bean breeding programs. However, there is currently no available information on the transcriptome of faba bean responding to O. foetida parasitism. In this study, we employed RNA sequencing to explore the global gene expression changes associated with compatible and incompatible V. faba/O. foetida interactions. In this perspective, two faba bean varieties (susceptible and resistant) were examined at the root level across three stages of O. foetida development (Before Germination (BG), After Germination (AG) and Tubercule Stage (TS)). Our analyses presented an exploration of the transcriptomic profile, including comprehensive assessments of differential gene expression and Gene Ontology (GO) enrichment analyses. Specifically, we investigated key pathways revealing the complexity of molecular responses to O. foetida attack. In this study, we detected differential gene expression of pathways associated with secondary metabolites: flavonoids, auxin, thiamine, and jasmonic acid. To enhance our understanding of the global changes in V. faba response to O. foetida, we specifically examined WRKY genes known to play a role in plant host-parasitic plant interactions. Furthermore, considering the pivotal role of parasitic plant seed germination in this interaction, we investigated genes involved in the orobanchol biosynthesis pathway. Interestingly, we detected the gene expression of VuCYP722C homolog, coding for a key enzyme involved in orobanchol biosynthesis, exclusively in the susceptible host. Clearly, this study enriches our understanding of the V. faba/O. foetida interaction, shedding light on the main differences between susceptible and resistant faba bean varieties during O. foetida infestation at the gene expression level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boukteb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The Toll-like receptor 4 (TLR4), an important member of the host's innate immune response, is coded by a polymorphic gene. This polymorphism could be a predisposing factor for NasoPharyngeal Carcinoma (NPC)., Aim: To determine the association between TLR4 gene polymorphisms and the susceptibility to NPC in a cohort of Tunisian affected patients., Methods: Genomic DNAs from 245 unrelated patients affected by undifferentiated carcinoma type (UCNT) and 264 unrelated healthy controls were genotyped for the five single nucleotides polymorphisms (SNPs) of TLR4 locus (4434 A>G (rs1927914),7263 G>C (rs10759932), 6134 A>G(rs4986790), 8851C>T (rs 4986791), 5272 T>C(rs11536889), +8469 T>C (rs11536891)) by Taqman® 5'-nuclease assay., Results: Among all polymorphisms studied, only the rs4986790 G and rs4986791 T alleles were significantly more prevalent in patients' group than controls (45% vs. 38%; p=0.03; pc=0.06) and increased the risk of the NPC (OR=1.3, 95% CI=1.01-1.69). Also, we found that the frequency of the rs4986790 AA and rs4986791 TT genotypes was significantly higher in controls than in patients (25.7% vs 37%; p=0.006, pc=0.02) and conferred a protector factor in NPC (OR= 0.59, 95% CI= 0.39-0.87). Further, based on the Kaplan-Meier survival curve we observed also the positive effect ofrs1927914 AA genotype on a prognostic of NPC (p=0.006; pc=0.01)., Conclusion: Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.

In this current study, we explored the preventive capacity of the aqueous extract of Orobanche foetida (OF), a root holoparasite, against CCl 4 prompt hepatotoxicity in rats. LC-MS/MS profiling revealed the existence of 32 compounds belonging to organic acids, benzoic acid derivatives, and hydroxycinnamic acids along with their glycosides and derivatives as well as several flavonoids. In vitro , OF demonstrated substantial antioxidant potential at DPPH and ABTS assays. Results showed that the pretreatment with OF for 6 weeks at the doses (25 mg/kg bw) and (50 mg/kg bw) countered the CCl 4 -induced liver injury by restoring liver injuries indicators (ALT, AST, LDH, ALP, GGT and bilirubin), normalizing lipid profile (TC, TG, LDL-C, and HDL-C), as well as, impeding DNA fragmentation. Furthermore, OF blocked the hepatic oxidative stress spurred by CCl 4 administration through boosting antioxidant enzymes (GSH, CAT, and SOD) responsible of diminishing lipid peroxidation. exhibited an anti-inflammatory effect by downregulating TNF-α and IL-6 levels. OF suppressive effect on proinflammatory cytokines is further exerted by its capacity to modulate the expression of the NF-κB gene. In silico investigation revealed that among the 32 identified compounds, vanillic acid glucoside and dihydroxybenzoic acid glucoside have strong and stable bindings with the active sites of three key inflammatory proteins (PARP-1, TNF-α, IL-6), which could highlight the antioxidant and anti-inflammatory capacity of. Overall, this research provides a preliminary pharmacological support for the medicinal applications of Orobanche foetida for addressing inflammatory and hepato-pathological conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bedoui, Mufti, Feriani, Baccari, Bouallegue, Kharrat, Sobeh, Amri and Abbes.)

Broomrapes ( Orobanche spp.) are root parasitic plants that threaten agricultural production in many parts of the world. In this study, the effect of two orobanche species, Orobanche crenata and O. foetida , on faba bean plants was studied in Tunisia. The two orobanche species inhibited both biomass production and pod formation, decreased the chlorophyll (Chl) content and total lipid (TL), and enhanced electrolyte leakage (EL) and lipid peroxidation. Concomitantly, orobanche parasitism induced a lower degree of fatty acid (FA) unsaturation due to a shift in the FA composition. On the other hand, with regard to orobanche seeds, oleic and linoleic acids were the predominant FA in the two orobanche species. After orobanche seed germination and penetration of host tissues, all the orobanche development stages showed a decrease in the TL content and changes in the FA composition in comparison to orobanche seeds. The level of TL was equal to or lower in all parasite development stages (except for S4) than that in the roots and leaves of healthy faba bean plants. These results suggest that the negative effect of orobanche infestation on faba bean development can be attributed to the reduced chlorophyll content and alteration in membrane stability attested by the reduced TL level and FA unsaturation.

Background: Food allergy (FA) has become a major public health concern affecting millions of children and adults worldwide. In Tunisia, published data on FA are scarce., Methods: This study, was intended to fill the gap and estimate the frequency of allergy to different foods in the Sfax region, Tunisia, within self-reported FA. One hundred twenty-five (125) children (56% males, 1-17 years old), and 306 adults (17% males, 18-70 years old) were interviewed using a bilingual questionnaire., Results: The number of self-reported food allergens in this sample was 105; allergens were clustered in 8 foods: fruits, seafood, eggs, milk and dairy, cereals, nuts, vegetables, and peanuts. Cutaneous reactions were the most frequent symptoms, in both children and adults. About 40% of children and 30% of adults had a family history of FA. About 81% of adults and 38% of children are allergic to at least 1 non-food allergen. The most prevalent food allergen was the fruit group in both adults and children, followed by seafood. Most food allergies were mutually exclusive and 90% of individuals have a single FA. The relationship between self-declared FA was modeled using a Bayesian network graphical model in order to estimate conditional probabilities of each FA when other FA is present., Conclusions: Our findings suggest that the prevalence of self-reported FA in Tunisia depends on dietary habits and food availability since the most frequent allergens are from foods that are highly consumed by the Tunisian population., Competing Interests: The authors have no conflict of interest to declare., (© 2023 The Authors.)

The purpose of this work was to investigate the structural, thermal, micromechanical and tribological properties of novel polymer/metal composite materials for bearing applications. Copper (Cu)-filled Acrylonitrile Butadiene Styrene (ABS) composites were mixed in a laboratory scale by an internal mixer with two blade impellers, and then injection-molded. Neat ABS, ABS+5wt% Cu, ABS+10wt% Cu, and ABS+15wt% Cu were the four materials that were tested. The dispersion of Cu particles in the ABS matrix was investigated using Scanning Electron Microscopy (SEM) and a micro-tomography scan. The filler particles have a uniform distribution in the matrix, according to the observations. The incorporation of Cu filler also refined an increase in the glass transition temperature from Differential Scanning Calorimetry (DSC) and less intensity in the amorphous phase by X-ray diffraction (XRD). Nanoindentation tests were carried out to characterize the micro-mechanical behavior of the composites. Friction and wear analysis were also examined using a pin-on-disk tribometer. Compared with neat ABS, all the micro-composites showed much higher indentation hardness, Vickers hardness, and indentation elastic modulus. It was also concluded that the incorporation of Cu filler into ABS simultaneously improved the friction and wear properties of the composites, which contributed to the suitability of the micro-filled composites with hard metallic particles for a wider range of mechanical components for bearing applications.

Purpose: The aim of this study was to evaluate corneal endothelial cell density and morphology, central corneal thickness, and best visual acuity using ultrasound (US) phacoemulsification or nanosecond laser technique., Setting: Department of ophthalmology, Nabeul, Tunisia., Design: Prospective cohort study., Methods: This study included eyes with nuclear cataracts with a density grade of 1, 2, 3, or 4 according to LOCS III, divided into two groups; group 1 had conventional US, and group 2 had nanosecond laser. The endothelial cell density (ECD), coefficient of variation (CoV) in cell size, percentage of hexagonal cells, central corneal thickness (CCT) and best visual acuity (VA) were evaluated during 24 months., Results: Seventy-four eyes had uneventful surgery, 40 in group 1, 34 in group 2. Three procedures in group 2 required conversion to standard phacoemulsification. The mean ECD decreased from 2616.4 ± 194.6 cells/mm 2 in group 1 preoperatively to 2088.4 ± 229.9 after 2 years. In group 2, it decreased from 2611.8 ± 186.5 cells/mm 2 to 2276.4 ± 163.8 after 2 years. The change was statistically significant in both groups. The decline of the mean ECD in group 2 was significantly less important than in group 1 ( p  = <10 -2 ). The mean percentage of hexagonal cells was 45.18 ± 4.9 preoperatively and 43.5% ± 6.6 after 2 years in group 1. In group 2, it remained almost stable with 45.6 ± 5.1 and 45.4% ± 6.6 preoperatively and after 2 years, respectively. Preoperatively, the mean CoV was 0.39 ± 0.037 in group 1 and 0.38 ± 0.04 in group 2. After 2 years, it was 0.38 ± 0.04 and 0.37 ± 0.038 in group 1 and group 2, respectively. The changes of the mean CoV and the mean percentage of hexagonal cells were significant in both groups, but the difference between the groups was significant only during the six first months postoperatively. In preoperative, the mean corneal central thickness was 509.7 ± 19.5 in group 1 and 510.3 ± 20.4 in group 2. In both groups, the mean corneal thickness increased on D1 postoperatively to 550.9 in group 1, and 528.2 in group 2. The mean corneal thickness decreased more rapidly after 1 week in group 2, to find the initial values. Visual acuity improved from 0.76 Log Mar ± 0.5 at enrolment to 0.45 Log Mar ± 0.2, and 0.033 Log Mar ± 0.086 in group 1 at 1 day post-operative and after 24 months, respectively and from 0.58 Log Mar ± 0.28 to 0.2 Log Mar ± 0.09 and 0.035 Log Mar ± 0.083, respectively in group 2. There was no significant difference in VA at each follow-up between groups except for day 1., Conclusion: Our study showed lower corneal tissue trauma, and lower endothelial cell loss in the laser cataract surgery compared to phacoemulsification. Clinical trial registration : (https://classic.clinicaltrials.gov/ct2/show/NCT05886283), identifier NCT05886283., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zbiba, Kharrat, Sayadi, Kallel and Marzouk.)

Faba bean ascochyta blight, caused by Ascochyta fabae Speg. (teleomorph: Didymella fabae Punith.), is one of the most devastating diseases of the crop. It can cause yield losses that reach 95% in conducive weather conditions. Surveys were carried out in five regions of Tunisia: Beja, Bizerte, Jendouba, Kef and Tunis-Cap Bon. A total of 513 fungal isolates were collected from 2011 to 2013. A molecular characterization was conducted to identify the mating type of each individual using a mating type specific PCR. Results revealed that the two mating types MAT1-2 and MAT1-1 coexisted in all surveyed regions. An imbalance in favor of MAT1-2 was observed particularly in Bizerte and Jendouba regions (sex ratio was 18:85 and 32:80, respectively). Moreover, morphological and pathogenic characterization of 122 isolates among the collection revealed a significant variability in conidia type (one celled or two celled conidia) frequency, in conidia mean size and in aggressiveness toward Badii faba bean cultivar (incubation period, IP; percentage necrotic leaf area, S; and area under disease progression curve, AUDPC). A principal component analysis (PCA) performed on morphologically studied parameters (frequency of conidia cell number and conidia mean size) identified three groups of isolates based on morphological traits: one celled (1C) and two celled (2C) conidia rates, one celled and two celled conidia length and width (1L, 1W, 2L and 2W, respectively). A second PCA using aggressiveness parameters (IP: Incubation period, S1, S4 and S9: percentage of necrotic leaf area respectively 5, 20 and 45 days after inoculation) identified three distinct pathogenic groups: poorly pathogenic AG1, moderately pathogenic AG2 and highly pathogenic AG3. Morphological and pathogenic groups and mating type data were used to conduct a multiple factorial correspondence analysis (MFCA) which revealed a correlation between the variables studied. Five groups were identified, each associated with a morphological and pathogenic trait and mating type. The most pathogenic group belonged to MAT1-2 suggesting that in locations where MAT1-2 is prevalent the epidemic risk is more important., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Omri Ben Youssef, Halila, Mbazia, Bessaidi, Missaoui, Kharrat and Le May.)

Beneficial microorganisms, including members of the Trichoderma genus, are known for their ability to promote plant growth and disease resistance, as well as being alternatives to synthetic inputs in agriculture. In this study, 111 Trichoderma strains were isolated from the rhizospheric soil of Florence Aurore, an ancient wheat variety that was cultivated in an organic farming system in Tunisia. A preliminary ITS analysis allowed us to cluster these 111 isolates into three main groups, T. harzianum (74 isolates), T. lixii (16 isolates) and T. sp. (21 isolates), represented by six different species. Their multi-locus analysis (tef1, translation elongation factor 1; rpb2, RNA polymerase B) identified three T. afroharzianum , one T. lixii , one T. atrobrunneum and one T. lentinulae species. These six new strains were selected to determine their suitability as plant growth promoters (PGP) and biocontrol agents (BCA) against Fusarium seedling blight disease (FSB) in wheat caused by Fusarium culmorum . All of the strains exhibited PGP abilities correlated to ammonia and indole-like compound production. In terms of biocontrol activity, all of the strains inhibited the development of F. culmorum in vitro, which is linked to the production of lytic enzymes, as well as diffusible and volatile organic compounds. An in planta assay was carried out on the seeds of a Tunisian modern wheat variety (Khiar) by coating them with Trichoderma . A significant increase in biomass was observed, which is associated with increased chlorophyll and nitrogen. An FSB bioprotective effect was confirmed for all strains (with Th01 being the most effective) by suppressing morbid symptoms in germinated seeds and seedlings, as well as by limiting F. culmorum aggressiveness on overall plant growth. Plant transcriptome analysis revealed that the isolates triggered several SA- and JA-dependent defense-encoding genes involved in F. culmorum resistance in the roots and leaves of three-week-old seedlings. This finding makes these strains very promising in promoting growth and controlling FSB disease in modern wheat varieties.

Baclofen is a β-(p-chlorophenyl) derivative of the neurotransmitter y-aminobutyrio acid (GABA). This centrally-acting GABA agonist is prescribed as therapy for spasticity in the spinal cord region. The drug is predominantly excreted by the kidney, thus making patients with kidney disease susceptible to side effects. We report on a patient with end-stage renal disease who developed baclofen toxicity, which was successfully treated with intense hemodialysis., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only ( p = 8.7 × 10 -3 ), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results.

Since the beginning of the Coronavirus disease-2019 pandemic, there has been a growing interest in exploring SARS-CoV-2 genetic variation to understand the origin and spread of the pandemic, improve diagnostic methods and develop the appropriate vaccines. The objective of this study was to identify the SARS-CoV-2s lineages circulating in Tunisia and to explore their amino acid signature in order to follow their genome dynamics. Whole genome sequencing and genetic analyses of fifty-eight SARS-CoV-2 samples collected during one-year between March 2020 and March 2021 from the National Influenza Center were performed using three sampling strategies.. Multiple lineage introductions were noted during the initial phase of the pandemic, including B.4, B.1.1, B.1.428.2, B.1.540 and B.1.1.189. Subsequently, lineages B1.160 (24.2%) and B1.177 (22.4%) were dominant throughout the year. The Alpha variant (B.1.1.7 lineage) was identified in February 2021 and firstly observed in the center of our country. In addition, A clear diversity of lineages was observed in the North of the country. A total of 335 mutations including 10 deletions were found. The SARS-CoV-2 proteins ORF1ab, Spike, ORF3a, and Nucleocapsid were observed as mutation hotspots with a mutation frequency exceeding 20%. The 2 most frequent mutations, D614G in S protein and P314L in Nsp12 appeared simultaneously and are often associated with increased viral infectivity. Interestingly, deletions in coding regions causing consequent deletions of amino acids and frame shifts were identified in NSP3, NSP6, S, E, ORF7a, ORF8 and N proteins. These findings contribute to define the COVID-19 outbreak in Tunisia. Despite the country's limited resources, surveillance of SARS-CoV-2 genomic variation should be continued to control the occurrence of new variants., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: Warburg Micro syndrome (WARBM) is a rare autosomal recessive genetic disease characterized by ocular, neurologic, and endocrine anomalies. WARBM is a phenotypically and genetically heterogeneous syndrome caused by mutations in RAB3GAP1 , RAB3GAP2 , RAB18 , and TBC1D20 . Here we present the clinical and genetic characterization of a consanguineous Tunisian family with a WARBM phenotype presenting two pathogenic variations, one of which is on RAB3GAP1 ., Methods: We applied whole-exome sequencing (WES) to two affected young males presenting a WARBM-compatible phenotype., Results: We reveal a new variation in RAB3GAP1 (NM&#95;012233.3: c.297del, p.Gln99fs) and another variation in ABCD1 (NM&#95;000033: c.896A>G, p.His299Arg). Each of these mutations, which in silico predictions concluded as being pathogenic variations, affects a critical protein region. Both affected males presented a WARBM-compatible phenotype, with severe intellectual disability, severe developmental delay, postnatal growth delay, postnatal microcephaly, congenital bilateral cataracts, general hypotonia, and a thin corpus callosum without a splenium. However, intrafamilial clinical heterogeneity was present, since only the oldest child had large ears, microphthalmia, foot deformities, and a genital anomaly, and only the youngest child had microcornea. Despite the mutation identified in ABCD1 , our patients did not have any X-linked symptoms of adrenoleukodystrophy disorder that are usually caused by ABCD1 mutations, which prompted our interest in clinical monitoring., Conclusions: WES analysis of a consanguineous Tunisian family with WARBM revealed a novel variation in RAB3GAP1 (NM&#95;012233.3: c.297del, p.Gln99fs) that is most likely pathogenic and allowed us to confirm the diagnosis of WARBM., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Korean Neurological Association.)

The aim of the present study was to extract starch from acorn ( Quercus suber L.) fruits using water and alkaline methods. Structural and functional properties of extracted starches were investigated and compared to those of corn and modified starches in order to determine their innovative potential application in food industry. The yield of extraction using the two methods was about 48.32% and 48.1%. The isolated starches showed low moisture, fat and protein contents, revealing high purity and quality. Additionally, the starch extracted using the alkaline method (AAS) showed higher lightness (60.41) when compared to starch isolated using hot water (WAS). However, the lightest white color was found for studied commercial starches. Moreover, AAS starch exhibited the highest swelling power, solubility and water absorption, followed by WAS and commercial starches. Results showed that extracted acorn starches were characterized by greater enthalpy and gelatinization temperatures. Similar observations were noted using FT-IR spectra analysis for all analyzed starches. In addition, granule starches observed using scanning electron microscopy were found to be spherical and ovoid. However, from the analysis by X-ray diffraction, a crystalline pattern of C-type was found for acorn starches, while commercial starches presented an A-type pattern. As an innovative food application, these underexploited acorn starches were valued and served to produce new custards with improved functional properties and better microstructure when compared to commercial custard.

Orobanche spp. are root parasitic plants that cause yield losses in faba bean (Vicia faba L.). In Tunisia, O. crenata and O. foetida are among the major problems limiting faba bean production and productivity. Breeding for resistance and development of resistant varieties remain the most efficient control strategy to combat these parasites. In our study, field trials were conducted over two consecutive cropping seasons. A set of 42 genotypes were used in this study; 39 advanced lines and three checks; Najeh and Baraca (resistant) and Badi (susceptible). The trials were conducted in highly infested O. foetida plot at Oued-Beja Research Station in Tunisia. Results showed that advanced lines XAR-VF00.13-1-2-1-2-1 and XBJ90.04-2-3-1-1-1-2A expressed high resistance level exceeding those recorded for resistance checks Najeh and Baraca. O. foetida significantly affected the biomass, grain yield, chlorophyll content index (CCI) and the maximum quantum efficiency (Fv/Fm ratio). No significant effect was observed on host plant water content (WC). CCI decreases varied from 46.4% for the susceptible check Badi and 4.2% and 9.3%, respectively, for Baraca and XBJ90.04-2-3-1-1-1-2A. Orobanche parasitism resulted in a slight decreases of Fv/Fm ratio for the advanced lines XBJ90.04-2-3-1-1-1-2A and XAR-VF00.13-1-2-1-2-1 against important decreases observed for Badi and Baraca. Correlation between resistance to O. foetida and CCI and Fv/Fm makes this, easy-to-measure, parameter very useful as a practical screening tool for early parasitism detection, diagnosis and identification and selection of high resistant plants against this parasite., Competing Interests: The authors have declared that no competing interests exist.

Orobanche foetida Poiret is a holoparasitic plant that lacks chlorophyll and totally depending on its host for its growth. Orobanche foetida parasitizes host plant roots and extract nutrient and water via a haustorium. Although O. foetida distributes in the Mediterranean region as a wild plant parasite, it parasitizes faba bean causing serious damages which may reach 90% yield losses in Tunisia. Analysis of genetic diversity of the parasite is important to better understand its evolution and spread, remained largely unknown. In this work, we present the first study on genetic diversity and population structure using the robust technique Restriction-site-Associated DNA sequencing (RADseq) for Orobanche spp. We collected 244 samples of O. foetida from 18 faba bean fields in the north of Tunisia including 17 populations from the north-west and one population form the north-east. To overcome the difficulty of SNP discovery in O. foetida genome as a non-model and tetraploid plant, we utilized three different informatics pipelines, namely UNEAK, pyRAD and Stacks. This study showed that genetic differentiation occurred in the Tunisian O. foetida emphasizing the isolation by distance effect. However, no strong population clustering was detected in this work basing on the three data sets and clustering methods used. The present study shed the light on the current distribution and the genetic variation situation of the fetid broomrape in Tunisia, highlighting the importance of understanding the evolution of this parasite and its genetic background. This will aid in developing efficient strategies to control this parasite and its expansion in Tunisia and worldwide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boukteb, Sakaguchi, Ichihashi, Kharrat, Nagano, Shirasu and Bouhadida.)

Background: Coronavirus Disease 2019 (COVID-19) is a viral pandemic disease that may induce severe pneumonia in humans. In this paper, we investigated the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. Sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins were compared to identify similar patterns. The immunogenic effect of identified segments was, then, assessed using a combination of structural and antigenicity prediction tools., Results: A total of 14 highly similar segments were identified in the investigated vaccines. Structural and antigenicity prediction analysis showed that, among the identified patterns, three segments in Hepatitis B, Tetanus, and Measles proteins presented antigenic properties that can induce putative protective effect against COVID-19., Conclusions: Our results suggest a possible protective effect of HBV, Tetanus and Measles vaccines against COVID-19, which may explain the variation of the disease severity among regions.

Repetitive DNA sequences occupy the major proportion of DNA in the human genome and even in the other species' genomes. The importance of each repetitive DNA type depends on many factors: structural and functional roles, positions, lengths and numbers of these repetitions are clear examples. Conserving such DNA sequences or not in different locations in the chromosome remains a challenge for researchers in biology. Detecting their location despite their great variability and finding novel repetitive sequences remains a challenging task. To side-step this problem, we developed a new method based on signal and image processing tools. In fact, using this method we could find repetitive patterns in DNA images regardless of the repetition length. This new technique seems to be more efficient in detecting new repetitive sequences than bioinformatics tools. In fact, the classical tools present limited performances especially in case of mutations (insertion or deletion). However, modifying one or a few numbers of pixels in the image doesn't affect the global form of the repetitive pattern. As a consequence, we generated a new repetitive patterns database which contains tandem and dispersed repeated sequences. The highly repetitive sequences, we have identified in X and Y chromosomes, are shown to be located in other human chromosomes or in other genomes. The data we have generated is then taken as input to a Convolutional neural network classifier in order to classify them. The system we have constructed is efficient and gives an average of 94.4% as recognition score., (© 2020 Elsevier Ltd. All rights reserved.)

The Mediterranean region is identified as one of the world's 36 biodiversity hotspots, with the Earth's most biologically rich yet threatened areas. Lebanon is a hub for Eastern Mediterranean Region (EMR) biodiversity with 9116 characterized plant and animal species (4486 fauna and 4630 flora). Using DNA barcoding as a tool has become crucial in the accurate identification of species in multiple contexts. It can also complement species morphological descriptions, which will add to our understanding of the biodiversity and richness of ecosystems and benefit conservation projects for endangered and endemic species. In this study, we create the first reference library of standard DNA markers for mammals and plants in the EMR, with a focus on endemic and endangered species. Plant leaves were collected from different nature reserves in Mount Lebanon, and mammal samples were obtained from taxidermized museum specimens or road kills. We generated the 12S rRNA sequences of 18 mammal species from 6 orders and 13 different families. We also obtained the trnL and rbcL barcode sequences of 52 plant species from 24 different families. Twenty-five plant species and two mammal species included in this study were sequenced for the first time using these markers.

Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including Bat, Yak and Pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from Bat and Pangolin strains. This study offers new ways to automatically characterize viruses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this study, a new starch has been isolated from acorn ( Quercus ilex ) fruits. The chemical composition of acorn flour showed its richness in carbohydrates (64.43%), proteins (8%), and fat (10%). The extraction yield of acorn starch was about 34.5%. Thus, the composition of extracted acorn starch and its physical and functional properties were studied. Acorn starch had high purity represented by low proportions of proteins (0.92%) and lipids (0.51%) with a pH of 5.3. The swelling power was 20.76 g/g, while the solubility was about 64.22% at 90°C which suggests that acorn starch has potential for use in food industries. The FT-IR spectra of isolated native starches have shown the main bands characterizing the starch. However, X-ray diffractograms exhibited an A- and B-type diffraction pattern. Furthermore, the effect of acorn starch incorporation at different levels (0.5%, 1%, 1.5%, and 2%) on the quality parameters of a fermented dairy product was investigated at the beginning of storage. The results demonstrated that the most suitable dose of acorn starch to be incorporated in the fermented dairy product was lower than 1%. This low concentration reduced syneresis, improved functional properties, and enhanced the viscosity of the fermented dairy product., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Youkabed Zarroug et al.)

DNA hypomethylation of long interspersed repetitive DNA retrotransposon (LINE-1) and Alu repeats elements of short interspersed elements family (SINEs) is an early event in carcinogenesis that causes transcriptional activation and leads to chromosomal instability. In the current study, DNA methylation levels of LINE-1 and Alu repeats were analyzed in tumoral tissues of invasive breast cancer in a Tunisian cohort and its association with the clinicopathological features of patients was defined. DNA methylation of LINE-1 and Alu repeats were analyzed using pyrosequencing in 61 invasive breast cancers. Median values observed for DNA methylation of LINE-1 and Alu repeats were considered as the cut-off (59.81 and 18.49%, respectively). The results of the current study demonstrated a positive correlation between DNA methylation levels of LINE-1 and Alu repeats (rho=0.284; P<0.03). DNA hypomethylation of LINE-1 was also indicated to be associated with low grade (P=0.023). To the best of our knowledge, the current study is the first study regarding DNA methylation of LINE-1 and Alu repeats element in breast cancer of the Tunisian population. The results of the current study suggest that, since hypomethylation of LINE-1 is associated with low grade, it could be used as a biomarker for prognosis for patients with breast cancer., (Copyright © 2020, Spandidos Publications.)

Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the ventricular muscle without dilation and is often associated with dominant pathogenic variants in cardiac sarcomeric protein genes. Here, we report a family with two infants diagnosed with infantile-onset HCM and mitral valve dysplasia that led to death before one year of age. Using exome sequencing, we discovered that one of the affected children had a homozygous frameshift variant in Myosin light chain 2 (MYL2:NM&#95;000432.3:c.431&#95;432delCT: p.Pro144Argfs*57;MYL2-fs), which alters the last 20 amino acids of the protein and is predicted to impact the most C-terminal of the three EF-hand domains in MYL2. The parents are unaffected heterozygous carriers of the variant and the variant is absent in control cohorts from gnomAD. The absence of the phenotype in carriers and the infantile presentation of severe HCM is in contrast to HCM associated with dominant MYL2 variants. Immunohistochemical analysis of the ventricular muscle of the deceased patient with the MYL2-fs variant showed a marked reduction of MYL2 expression compared to an unaffected control. In vitro overexpression studies further indicate that the MYL2-fs variant is actively degraded. In contrast, an HCM-associated missense variant (MYL2:p.Gly162Arg) and three other MYL2 stop-gain variants (p.E22*, p.K62*, p.E97*) that result in loss of the EF domains are stably expressed but show impaired localization. The degradation of the MYL2-fs can be rescued by inhibiting the cell's proteasome function supporting a post-translational effect of the variant. In vivo rescue experiments with a Drosophila MYL2-homolog (Mlc2) knockdown model indicate that neither the MYL2-fs nor the MYL2:p.Gly162Arg variant supports normal cardiac function. The tools that we have generated provide a rapid screening platform for functional assessment of variants of unknown significance in MYL2. Our study supports an autosomal recessive model of inheritance for MYL2 loss-of-function variants in infantile HCM and highlights the variant-specific molecular differences found in MYL2-associated cardiomyopathy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The aim of this study was to evaluate the Immunoscore (IS) methodology as a prognostic marker of colorectal adenocarcinoma in Tunisian population. Tumor blocks were retrospectively collected from 106 patients with sporadic colorectal cancer., Methods: Immunohistochemical staining and images analysis software were used to quantify the density of CD3 + and CD8 + tumor-infiltrating lymphocytes in the center of the tumor and invasive margin., Results: The density of CD3 + and CD8 + was significantly associated with 5-year overall survival ( P =0.001 and P =0.00098, respectively) and 5-year disease-free survival ( P =0.0006 and P =0.0056, respectively). The earlier stage and the absence of vascular emboli showed a significant association with IS analysis. Cox multivariate regression analysis revealed that Immunoscore (from I0 to I4) was more significantly correlated with overall survival ( P =0.00011) and disease-free survival ( P =0.0008) than Tumor-Node-Metastasis (TNM) staging ( P =0.057 and P =0.039, respectively). Patients with low IS were associated with inferior disease-free survival and overall survival, contrary to patients with high IS., Conclusion: This is the first study which evaluated the prognostic value of IS methodology in colorectal cancer in African and Arabic population. The IS methodology carries out in this study allows to estimate the risk of relapse in patients with colorectal cancer. Overall, our results support the implementation of the consensus Immunoscore as a new component for the classification of cancer, designated TNM-Immune., Competing Interests: The authors declare that they have no competing interests in this work., (© 2019 Trabelsi et al.)

Therapeutic resistance is a major clinical challenge in oncology. Evidence identifies cancer stem cells (CSCs) as a driver of tumor evolution. Accordingly, the key stemness property unique to CSCs may represent a reservoir of therapeutic target to improve cancer treatment. Here, we carried out a genome-wide RNA interference screen to identify genes that regulate breast CSCs-fate (bCSC). Using an interactome/regulome analysis, we integrated screen results in a functional mapping of the CSC-related processes. This network analysis uncovered potential therapeutic targets controlling bCSC-fate. We tested a panel of 15 compounds targeting these regulators. We showed that mifepristone, salinomycin, and JQ1 represent the best anti-bCSC activity. A combination assay revealed a synergistic interaction of salinomycin/JQ1 association to deplete the bCSC population. Treatment of primary breast cancer xenografts with this combination reduced the tumor-initiating cell population and limited metastatic development. The clinical relevance of our findings was reinforced by an association between the expression of the bCSC-related networks and patient prognosis. Targeting bCSCs with salinomycin/JQ1 combination provides the basis for a new therapeutic approach in the treatment of breast cancer., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)