Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach.

The aim of this study was to elucidate the redox effects of Thiophanate methyl (MT) in the rat liver and kidney. Our results showed, after 3 days of MT injection (700 mg/kg), an increase in malondialdehyde (MDA), hydrogen peroxide and advanced oxidation protein products levels. Glutathione peroxidase and superoxide dismutase activities were also remarkably increased in the liver but decrease in the kidney. Glutathione and vitamin C values were significantly reduced. The changes in biochemical parameters were substantiated by histological and molecular data. A smear without ladder formation on agarose gel was shown, indicating random DNA degradation in the liver and the kidney of MT treated rats. The increase in cyclooxygenase-2 gene expression, marker of inflammation, and an increase in genes expression of glutathione peroxidase and superoxide dismutase in liver and their decrease in the kidney were also occurred after MT exposure. These data confirmed the pro-oxidant and genotoxic effects of this fungicide.

Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats.

Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.

Effect of novel curcumin-encapsulated chitosan-bioglass drug on bone and skin repair after gamma radiation: experimental study on a Wistar rat model.

Radiation therapy contributes to a significant increase in bone osteoporosis and skin loss. Various natural health products might be beneficial to reduce bone and skin alterations. Curcumin (CUR) medicines derived from natural plants have played an important role in health care. This study aims at synthesizing and evaluating the performance therapy of CUR-encapsulated bioglass-chitosan (CUR-BG-CH). In vitro, the antioxidant assay was evaluated by using 1,1-diphenyl-2-picrylhydrazyl free-radical (DPPH) scavenging and the nitroblue tetrazolium reduction. The CUR-BG-CH antimicrobial effects were tested in liquid media. In vivo, after rat (60) Co γ-radiation, the tissue wound-healing process was studied by grafting CUR and CUR-BG-CH in femoral condyle and dorsal skin rat tissue. The antioxidant studies indicated that CUR-BG-CH quenches free radicals more efficiently than unmodified CUR and had effective DPPH (91%) and superoxide anion (51%) radical scavenging activities. The CUR-BG-CH biomaterial exhibited an important antimicrobial activity against Staphylococcus aureus. The histomorphometric parameters showed amelioration in CUR-BG-CH-treated rats. An improved mechanical property was noticed (33.16 ± 5.0 HV) when compared with that of unmodified CUR group (23.15 ± 4.9 HV). A significant decrease in tumour necrosis factor-α cytokine production was noted in the CUR-BG-CH rats (90 pg/ml) as compared with that of unmodified CUR group (240 pg/ml). The total amount of hydroxyproline was significantly enhanced (33.5%) in CUR-BG-CH group as compared with that of control. Our findings suggested that CUR-BG-CH might have promising potential applications for wound healing.

Detoxification of rats subjected to nickel chloride by a biomaterial-based carbonated orthophosphate.

Recently, the therapeutic approaches of the detoxification against the metals (nickel) in the body are the use of biomaterials such as carbonated hydroxyapatite. The aim of this study is therefore to analyze the physiological and physicochemical parameters of strain white rats "Wistar" receiving nickel chloride and to study the protective associative of apatite against adverse effects of this metal, and this in comparison with control rats. Our results showed that the nickel induced in rats an oxidative stress objectified by elevated levels of thiobarbituric acid-reactive substances and conjugated dienes associated with inhibition of the activity of the antioxidant defense system such as glutathione peroxidase, superoxide dismutase and catalase in the liver, kidney, spleen and erythrocyte. Disorders balances of ferric, phosphocalcic, a renal failure and a liver toxicity were observed in rats exposed to nickel. As well as a significant increase in the rate of nickel in the bones and microcytic anemia was revealed. However, the implantation of carbonated hydroxyapatite in capsule form protects rats intoxicated by the nickel against the toxic effects of this metal by lowering the levels of markers of lipid peroxidation and improving the activities of defense enzymes. Our implantation technique is effective to correct ferric balance and phosphocalcic equilibrium, to protect liver and kidney function, to reduce the rate of bone nickel and to correct anemia. They clearly explain the beneficial and protective of our biomaterial which aims the detoxification of rats receiving nickel by substituting cationic (Ca(2+) by Ni(2+)) and anionic (OH(-) by Cl(-)) confirmed by physicochemical characterization like the IR spectroscopy and X-ray diffraction. These techniques have shown on the one hand a duplication of OH(-) bands (IR) and on the other hand the increase of the volume of the apatite cell after these substitutions (X-ray diffraction).

Horizons in Endometriosis: Proceedings of the Montreux Reproductive Summit, 14-15 July 2023.

Endometriosis is a complex and chronic gynaecological disorder that affects millions of women worldwide, leading to significant morbidity and impacting reproductive health. This condition affects up to 10% of women of reproductive age and is characterised by the presence of endometrial-like tissue outside the uterus, potentially leading to symptoms such as chronic pelvic pain, dysmenorrhoea, dyspareunia, and infertility. The Montreux summit brought a number of experts in this field together to provide a platform for discussion and exchange of ideas. These proceedings summarise the six main topics that were discussed at this summit to shed light on future directions of endometriosis classification, diagnosis, and therapeutical management. The first question addressed the possibility of preventing endometriosis in the future by identifying risk factors, genetic predispositions, and further understanding of the pathophysiology of the condition to develop targeted interventions. The clinical presentation of endometriosis is varied, and the correlation between symptoms severity and disease extent is unclear. While there is currently no universally accepted optimal classification system for endometriosis, several attempts striving towards its optimisation - each with its own advantages and limitations - were discussed. The ideal classification should be able to reconcile disease status based on the various diagnostic tools, and prognosis to guide proper patient tailored management. Regarding diagnosis, we focused on future tools and critically discussed emerging approaches aimed at reducing diagnostic delay. Preserving fertility in endometriosis patients was another debatable aspect of management that was reviewed. Moreover, besides current treatment modalities, potential novel medical therapies that can target underlying mechanisms, provide effective symptom relief, and minimise side effects in endometriotic patients were considered, including hormonal therapies, immunomodulation, and regenerative medicine. Finally, the question of hormonal substitution therapy after radical treatment for endometriosis was debated, weighing the benefits of hormone replacement.

Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats.

New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity.

Accessory and cavitated uterine masses: a case series and review of the literature.

Objectives: The purpose of this study is to report nine patients of young women who underwent a surgical treatment of an accessory and cavitated uterine mass (ACUM) in our hospital between 2014 and 2022 and review all cases described in the literature. Material and methods: The principal outcomes measured are the imaging techniques used to determine the diagnosis, the type of surgery used and the post-operative evolution of symptoms. We also report and analyse the 79 patients found in the literature since 1996 in addition to our 9 patients. Results: Surgical excision is the only long-lasting treatment. Small invasive surgery with laparoscopic access is the gold standard and most widely used (83.0%). Some new therapeutic procedures have been recently described of which ethanol sclerotherapy seems very promising. Post-operatively, 54.5% of patients have a complete relief of symptoms. MRI is the best imaging technique to identify ACUM. Finally, we refine the description of this pathology and give a more precise definition of it. Conclusion: Through our literature review and the analysis of our cases, we want to underline an important diagnostic criterion of this pathology: the fallopian tube on the homolateral side of the ACUM never communicates with the latter. It is a capital element for differential diagnosis.

Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice.

Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.

Isolation of rat embryonic stem-like cells: a tool for stem cell research and drug discovery.

The establishment of rat embryonic stem cells constitutes a precious tool since rat has been extensively used in biomedical research, in particular for the generation of human neurodisease animal models. Up to now only a few studies have described the isolation of rat embryonic stem-like cells. One out of 9 isolated rat embryonic stem-like cell lines (B1-RESC) obtained from a 4.5-day post-coitum blastocyst were extensively characterized and kept in culture for up to 80 passages on feeders with LIF. The stable growth of these cells and the expression of pluripotent markers were confirmed up to a high number of passages in culture, also in the absence of feeders and LIF. B1-RESC expresses the three germ layers markers both in vitro, within differentiating embryoid bodies, and in vivo through teratoma formation. Collectively, the B1-RESC line with a stable near-diploid karyotype can be used as a highly sensitive tool for testing anti-proliferative molecules.

Thrombocytopaenia in pregnancy: the importance of differential diagnosis during the COVID-19 pandemic.

Since the beginning of the COVID-19 pandemic, an optimal management of vulnerable patients, such as pregnant women, has been regarded as a challenge for healthcare professionals. Although thrombocytopaenia is considered a minor criterion for admission within an intensive care unit, a low platelet count has been observed in COVID-19 patients, including a pregnant woman, who developed severe pulmonary complications. Furthermore, thrombocytopaenia has been proposed as a potential biomarker in order to identify cases at high-risk complications. Nevertheless, thrombocytopaenia is a relatively frequent condition observed in pregnancy. In this context, a differential diagnosis is essential for the correct management of COVID-19 pregnant women.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats.

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

Biological activities and wound healing potential of a water-soluble polysaccharide isolated from Glycyrrhiza glabra in Wistar rat.

The present study aimed to evaluate the in vitro antibacterial and antioxidant activities and the in vivo wound healing performance of a polysaccharide isolated from Glycyrrhiza glabra named PSG. It was structurally characterized by Fourier transformed infrared (FT-IR) spectroscopy, which confirmed the presence of different polysaccharides functional bands. The antioxidant capacity of PSG was determined in vitro and evaluated in vivo through the examination of wound healing capacity. Thirty two rats were randomly divided into four groups: group I was treated with physiological serum (negative control); group II was treated with "CYTOL CENTELLA®"; group III was treated with glycerol and group IV was treated with polysaccharide. The response to treatments was assessed by macroscopic, histologic, and biochemical parameters. Data revealed that our sample exhibited potential antioxidant activities and accelerated significantly the wound healing process, after ten days of treatment, proved by the higher wound appearance scores and a higher content of collagen confirmed by histological examination, when compared with control and "CYTOL CENTELLA®". Overall, these findings proved that this polysaccharide isolated from Glycyrrhiza glabra could be considered as a natural bioactive polymer for therapeutic process in wound healing applications.

NANOG priming before full reprogramming may generate germ cell tumours.

Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

Dental pulp stem cells, niches, and notch signaling in tooth injury.

Stem cells guarantee tissue repair and regeneration throughout life. The decision between cell self-renewal and differentiation is influenced by a specialized microenvironment called the 'stem cell niche'. In the tooth, stem cell niches are formed at specific anatomic locations of the dental pulp. The microenvironment of these niches regulates how dental pulp stem cell populations participate in tissue maintenance, repair, and regeneration. Signaling molecules such as Notch proteins are important regulators of stem cell function, with various capacities to induce proliferation or differentiation. Dental injuries often lead to odontoblast apoptosis, which triggers activation of dental pulp stem cells followed by their proliferation, migration, and differentiation into odontoblast-like cells, which elaborate a reparative dentin. Better knowledge of the regulation of dental pulp stem cells within their niches in pathological conditions will aid in the development of novel treatments for dental tissue repair and regeneration.

Potential Hepatoprotective Effect of Cheatomorpha gracilis extract against High Fat Diet (HFD)-Induced Liver Damage, and its characterization by HPLC.

The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and ß1 decreases / ß2 and γ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.

An in vitro study on reproductive toxicology of Deltamethrin on rat spermatozoa.

Recent findings indicate that synthetic pyrethroid insecticide may induce toxic manifestations by enhancing the production of reactive oxygen species and disrupting the balance between pro-oxidants and antioxidants as a result of lipid peroxidation (LP) of cell membranes. The aim of the study was to examine the potency of Deltamethrin (Del) to induce oxidative stress response in rat spermatozoa in vitro. Spermatozoa were incubated with different concentrations (0, 10, 50, 100 and 200 microm) of Del for 3 h at 37 degrees C. After that, sperm parameters (motility, viability and abnormal morphology), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined. We found that in vitro exposure to Del caused a significant decline of sperm motility and viability and increase of abnormal sperm morphology, MDA, SOD and CAT levels at different concentrations of Del. This study demonstrated that Del caused deterioration in sperm motility and viability, and induction in LP, abnormal morphology of spermatozoa and antioxidants enzyme activities.

Protective effects of spirulina against hemato-biochemical alterations, nephrotoxicity, and DNA damage upon lead exposition.

The current study was aimed at exploring the protective efficacy of spirulina against the hemato-biochemical alterations and nephrotoxicity induced by lead (Pb). Female rats aged 12 weeks were treated for 4 weeks with Pb (0.344 g kg-1 bw) associated or not with spirulina (5.3 g kg-1 bw). Renal damage induced by Pb was related to a severe anemia, increases of oxidative stress-related parameters (thiobarbituric acid reactive substances (TBARS) (+29%), protein carbonyl (PCO) (+66.3%), and advanced oxidation protein product (AOPP) (+110%)), plasma lactate dehydrogenase (LDH) (+80%), creatinine and urea levels in plasma, and uric acid concentration in urine, as well as genotoxic changes (+89.3% and +60% for DNA and mRNA levels, respectively). Conversely, LDH and antioxidant enzyme activities in kidney were decreased, as well as the levels of plasma uric acid, and urinary creatinine and urea levels. Spirulina-supplemented rats exhibited normal peripheral blood and renal parameters and renal histology. It can be suggested that Arthrospira platensis alleviates damages induced by Pb, thanks to its high phenolic content and antioxidant capacity.

Rare case of remission of a patient with small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) stage IV: Case report.

INTRODUCTION: Small cell carcinoma of the ovary (SCC) is a very rare (less than 1 % of ovarien neoplasia), highly undifferentiated, aggressive malignancy affecting young women and linked to a poor prognosis. Overall survive rate is very low (about 16 %). SCCOHT has recently been shown to be associated with SMARCA4 gene mutations and shows some genetic similarities to malignant rhabdoid tumors (MRT). PRESENTATION OF CASE: After a reminder of the clinical, histological description of the SCCOHT and concensus about the medical management, we describe the rare case of a 22 years old patient with complete remission after diagnosis of un undifferentiated SCCOHT stage IV treated by conservative surgery and high-doses chemotherapy, 30 months after diagnosis. DISCUSSION: Thus far, no standard therapy exists for SCCOHT. Treatment modalities are surgery, chemotherapy, radiotherapy and autologous stem cell transplant after high-dose chemotherapy. Research for new treatments includes target therapy. CONCLUSION: Autologous stem cell transplant after high-dose adjuvant chemotherapy seems to lead to the best survival rates. Invasiveness of the treatment depends on the stage of the disease, age of the patient and her fertility-sparing desire. An international collaboration will be needed to standardise practices due of the small number of patients.

Long-term exposure to low lithium concentrations stimulates proliferation, modifies stress protein expression pattern and enhances resistance to oxidative stress in SH-SY5Y cells.

SH-SY5Y cells, derived from a human neuroblastoma, were submitted to short- or long-term exposures to lithium carbonate concentrations ranging from 0.5 to 8 mM. Short-term exposures (4 days) to concentrations higher than 6 mM were found to reduce cell growth rate while exposure to 8 mM resulted in significant cell mortality. These ranges of concentrations induced an overexpression of (1) the HSP27 stress protein, (2) a 108 kDa protein (P108) recognized by an anti-phospho-HSP27(Ser78) antibody, and probably corresponding to a phosphorylated HSP27 tetramer, (3) a 105 kDa protein (P105), possible glycosylated or phosphorylated form of the GRP94 stress protein and (4) a phosphorylated (inactivated) form of glycogen synthase kinase (GSK3alpha/beta) SH-SY5Y cells, when cultured in the presence of 0.5 mM lithium for 25 weeks, displayed interesting features as compared to controls: (1) higher cell growth rate, (2) increased resistance toward the inhibitory effects of high lithium concentrations on cell proliferation, (3) lower basal level of lipid peroxidation (TBARS) and improved tolerance to oxidative stress induced by high lithium concentrations, (5) reduced expression of monomeric HSP27 versus an increase of corresponding tetrameric protein (P108) and (6) overexpression of a 105 kDa protein (P105). In conclusion, our study suggests that chronic treatment (over several months) by therapeutic relevant lithium concentrations could favour neurogenesis, decrease the vulnerability of neuronal cells to oxidative stress and induce posttranslational changes of molecular chaperones.