Uncovering the Therapeutic Potential of Phosphocreatine in Diabetic Retinopathy: Mitigating Mitochondrial Dysfunction and Apoptosis via JAK2/STAT3 Signaling Pathway.

Diabetic retinopathy (DR) stands as a prevalent complication of diabetes mellitus, causing damage to the delicate retinal capillaries and potentially leading to visual impairment. While the exact underlying cause of DR remains elusive, compelling research suggests that mitochondrial energy deficiency and the excessive generation of reactive oxygen species (ROS) play pivotal roles in its pathogenesis. Recognizing that controlling hyperglycemia alone fails to reverse the defects in retinal mitochondria induced by diabetes, current strategies seek to restore mitochondrial function as a means of safeguarding against DR. To address this pressing issue, a comprehensive study was undertaken to explore the potential of phosphocreatine (PCr) in bolstering mitochondrial bioenergetics and providing protection against DR via modulation of the JAK2/STAT3 signaling pathway. Employing rat mitochondria and RGC-5 cells, the investigation meticulously assessed the impact of PCr on ROS production, mitochondrial membrane potential, as well as the expression of crucial apoptotic and JAK2/STAT3 signaling pathway proteins, utilizing cutting-edge techniques such as high-resolution respirometry and western blotting. The remarkable outcomes revealed that PCr exerts a profound protective influence against DR by enhancing mitochondrial function and alleviating diabetes-associated symptoms and biochemical markers. Notably, PCr administration resulted in an upregulation of antiapoptotic proteins, concomitant with a downregulation of proapoptotic proteins and the JAK2/STAT3 signaling pathway. These significant findings firmly establish PCr as a potential therapeutic avenue for combating diabetic retinopathy. By augmenting mitochondrial function and exerting antiapoptotic effects via the JAK2/STAT3 signaling pathway, PCr demonstrates promising efficacy both in vivo and in vitro, particularly in counteracting the oxidative stress engendered by hyperglycemia. In summary, our study sheds light on the potential of PCr as an innovative therapeutic strategy for diabetic retinopathy. By bolstering mitochondrial function and exerting protective effects via the modulation of the JAK2/STAT3 signaling pathway, PCr holds immense promise in ameliorating the impact of DR in the face of oxidative stress induced by hyperglycemia.

Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby Sex.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The convergence of the maternal and fetal circulations occurs in the placenta, which is the first organ to develop. Placental pathology provides an accurate diagnosis of amniotic sac inflammation, and pathological alterations in preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospective study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department at our institution. Thirty-seven male and forty-seven female placentas were collected following full-term delivery, and the grading and staging of any evident inflammatory responses were evaluated and correlated with the babies' sex. Full-thickness placental samples that were considered normal and not sent to the histopathology department were obtained from the central and marginal regions of placental discs. Morphological examination of the fresh placenta was conducted, and fetal and maternal inflammatory response syndromes were assessed. In addition, placental villitis of unknown etiology (VUE) and chronic deciduitis were evaluated. Immunohistochemistry was performed to evaluate the patterns of inflammation in the placenta using anti-CD8 and anti-CD68 antibodies. The correlation between silent pathologies and clinical complications or the development of fetal inflammatory response syndrome was measured. In this study, 17 (20%) maternal and 10 (12%) fetal samples showed inflammatory responses. The frequencies of chronic deciduitis and VUE were higher among pregnant Saudi women than previously reported, probably because fetal inflammatory response syndrome goes unnoticed in Saudi Arabia. In addition, the prevalence of fetal and maternal inflammatory responses was higher in the placentas of the mothers of males than in those of females, suggesting that differences occur in the inflammatory response in the placenta depending on the sex of the newborn. Grading placental inflammation (in cases of VUE) typically predicts the degree of maternal anti-fetal cellular rejection; therefore, increasing the number of placental samples sent for microscopic inspection may be preferable because of their significance in identifying the causes of chronic disorders.

Early-Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery.

Mycotoxins are produced by more than one hundred fungi and produce secondary metabolites that contaminate various agricultural commodities, especially rice and corn. Their presence in the food chain is considered a serious problem worldwide. In recent years, a link between exposure to mycotoxins and impaired fertility has been suggested. Consequently, it has become vital to investigate the interactive effects of these mycotoxins on ovarian function. In this study, we investigated the intergenerational effects of the mycotoxin fumonisin B1 (FB1) on ovarian structure and function. Virgin Wistar albino female rats were separated into control and FB1 treatment groups and examined from day 6 of pregnancy until delivery (20 and 50 mg/kg b.w./day). The obtained female rats of the first (F1) and second generations (F2) were euthanized at 4 weeks of age, and ovary samples were collected. We found that the ovary weight index increased with the high dose of the treatment (50 mg/kg b.w./day) among both F1 and F2, in a manner similar to that observed in polycystic ovary syndrome. As expected, FB1 at a high dose (50 mg/kg b.w.) reduced the number of primordial follicles in F1 and F2, leading to an accelerated age-related decline in reproductive capacity. Moreover, it reduced the fertility rate among the F1 female rats by affecting follicle growth and development, as the number of secondary and tertiary follicles decreased. Histopathological changes were evidenced by the altered structures of most of the growing follicle oocytes, as revealed by a thinning irregular zona pellucida and pyknosis in granulosa cells. These findings are concomitant with steroidogenesis- and folliculogenesis-related gene expression, as evidenced by the decrease in CYP19 activity and estrogen receptor beta (ESR2) gene expression. Additionally, GDF-9 mRNA levels were significantly decreased, and IGF-1 mRNA levels were significantly increased. However, the results from the ovaries of the F2 treatment groups were different and unexpected. While there was no significant variation in CYP19 activity compared to the control, the ESR2 significantly increased, leading to stereological and histopathological changes similar to those of the control, except for some altered follicles. The hallmark histological feature was the appearance of vacuolar structures within the oocyte and between granulosa cell layers. Interestingly, the autophagic marker LC3 was significantly increased in the F2 offspring, whereas this protein was significantly decreased in the F1 offspring. Therefore, we suggest that the promotion of autophagy in the ovaries of the F2 offspring may be considered a recovery mechanism from the effect of prenatal FB1 exposure. Thus, autophagy corrected the effect of FB1 during the early life of the F1 female rats, leading to F2 offspring with ovarian structure and function similar to those of the control. However, the offspring, treated female rats may experience early ovarian aging because their ovarian pool was affected.

Involvement of Autophagy and Oxidative Stress-Mediated DNA Hypomethylation in Transgenerational Nephrotoxicity Induced in Rats by the Mycotoxin Fumonisin B1.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation.

Hyperhalophilic Diatom Extract Protects against Lead-Induced Oxidative Stress in Rats and Human HepG2 and HEK293 Cells.

This work investigated the protective effects of microalga Halamphora sp. extract (HExt), a nutraceutical and pharmacological natural product, on human lead-intoxicated liver and kidney cells in vitro and in vivo in Wistar rats. The human hepatocellular carcinoma cell line HepG2 and the human embryonic kidney cell line HEK293 were used for the in vitro study. The analysis of the fatty acid methyl esters in the extract was performed via GC/MS. The cells were pretreated with HExt at 100 µg mL-1, followed by treatment with different concentrations of lead acetate, ranging from 25 to 200 µM for 24 h. The cultures were incubated (5% CO, 37 °C) for 24 h. Four groups, each containing six rats, were used for the in vivo experiment. The rats were exposed to subchronic treatment with a low dose of lead acetate (5 mg kg-1 b.w. per day). Pretreating HepG2 and HEK293 cells with the extract (100 µg mL-1) significantly (p < 0.05) protected against the cytotoxicity induced by lead exposure. For the in vivo experiment, the biochemical parameters in serum-namely, the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were measured in the organ homogenate supernatants. HExt was found to be rich in fatty acids, mainly palmitic and palmitoleic acids (29.464% and 42.066%, respectively). In both the in vitro and in vivo experiments, cotreatment with HExt protected the liver and kidney cell structures and significantly preserved the normal antioxidant and biochemical parameters in rats. This study discovered the possible protective effect of HExt, which could be beneficial for Pb-intoxicated cells.

Using autophagy, apoptosis, cytoskeleton, and epigenetics markers to investigate the origin of infertility in ex-fissiparous freshwater planarian individuals (nomen nudum species) with hyperplasic ovaries.

The origin of the sterility observed in ex-fissiparous freshwater planarians with hyperplasic ovaries has yet to be explained. To improve our understanding of this enigmatic phenomenon, immunofluorescence staining and confocal microscopy examination were used the assess autophagy, apoptosis, cytoskeleton, and epigenetics markers in the hyperplasic ovaries of ex-fissiparous individuals and the normal ovaries of sexual individuals. Immunofluorescence positivity for the autophagic marker microtubule-associated protein 1 light chain 3 (LC3) was significantly lower in the hyperplasic ovary than in the normal ovary. Compared with the normal ovary, the hyperplasic ovary exhibited significantly higher immunofluorescence positivity for the apoptotic marker caspase 3, suggesting that autophagy and apoptosis are closely associated in this pathogenicity. Furthermore, the level of global DNA (cytosine-5)-methyltransferase 3A (DNMT3) protein expression was significantly higher in the normal ovary than in the hyperplasic ovary, suggesting that DNA methylation is involved in the infertility phenomenon. The cytoskeleton marker actin also exhibited relatively higher immunofluorescence intensity in the normal ovary than in the hyperplasic ovary, consistent with previous findings on the role of cytoskeleton architecture in oocyte maturation. These results help improve our understanding of the causes of infertility in ex-fissiparous planarians with hyperplasic ovaries and provide new insights that will facilitate future studies on this mysterious pathogenicity.

Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus.

BACKGROUND: The annual prevalence of gestational diabetes mellitus-characterized by an increase in blood glucose in pregnant women-has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. METHODS: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. RESULTS: The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. CONCLUSIONS: Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life.

Effects of an Endocrine Disruptor Triclosan on Ruditapes decussatus: Multimarker and Histological Approaches.

The aim of this work was to study the ecotoxicological effects of an endocrine disruptor triclosan on the clam Ruditapes decussatus. The bivalves were exposed to three concentrations of this biocide (C1 = 100 ng/L, C2 = 200 ng/L and C3 = 500 ng/L) for three and seven days. The impact was assessed at the gills and digestive glands, through activities of an antioxidant defense biomarker (Gluthatione S-Transferase, GST), a damage biomarker (Malondialdehyde, MDA), and a neurotoxicity biomarker (Acetylcholinesterase, AChE). Furthermore, histological traits were approached in different organs to evaluate any possible alteration induced by triclosan. It appears from this study that both gills and digestive glands responded discernibly to triclosan and effects were concentration-dependent. The stressed clams showed a significant increase in their GST and MDA activities in gills and digestive glands compared to controls for both time slots considered. In turn, the AChE activity was clearly inhibited in both organs in a time dependent way. The histological study made it possible to observe several structural pathologies caused by triclosan in the gills and the digestive gland. These alterations consisted mainly of inflammatory reactions, malformations of the lamellae and fusion of the gill filaments, degeneration of the connective tissue, and the erosion of the gill cilia with the appearance of certain severe alterations (cell necrosis and apoptosis), which can thus cause a malfunction of the gills and eventually lead to a reduction in oxygen consumption and a disruption of the osmoregulation for bivalves. Alterations in the digestive gland have also been detected, mainly by epithelial alterations, thinning of the tubules, and alteration of the basal cell membrane which can impair the ability of clams to absorb food. At germinal cells, several damages were observed in the oocytes which probably disturbed the reproductive function and the fertility of the clams. The damages observed in female gonads were caused by the cytolysis of a large number of oocytes through autophagy and necrosis at 200 ng triclosan/L. Moreover, at 500 ng triclosan/L, hemocytic infiltration was observed in acini and apoptotic bodies reflected in the fragmentation of more than 90% of oocytes.

Stereological and histopathological assessment of intrauterine growth restriction placenta from Saudi women.

Background: Placental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR. Methods: Overall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques. Results: The IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group. Conclusion: The reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention.

In vivo evaluation and molecular docking studies of Schinus molle L. fruit extract protective effect against isoproterenol-induced infarction in rats.

The aim of the current study was to assess the potential cardiopreventive effect of the methanolic extract of S. molle L. (MESM) on isoproterenol-induced infarction in rats. The biomolecules content was evaluated using HPLC-DAD-ESI-QTOF-MS/MS analysis. On the 29th and 30th days, two successive injections of isoproterenol (ISO) were given to Wistar rats to provoke myocardial infarction following pretreatment with either MESM (60 mg/kg b.w) or Pidogrel (Pid; 2 mg/kg b.w.). A total of sixteen phenolics were identified with masazino-flavanone as the most prevalent compound (1726.12 µg/g dm). Results showed that MESM offered cardioprevention by normalizing the ST segment and reducing the elevated cardiac risk parameters. The altered lipid biomarkers together with the plasma ionic levels were improved. Additionally, MESM inhibited the cardiac oxidative stress generated by ISO injection though enhancing antioxidant enzymes (GSH, CAT, SOD and GPX) which reduced lipid peroxidation and protein oxidation. MESM reduced myocardial apoptosis by significantly repressing mRNA expressions of Caspase-3 and Bax, with an upregulated Bcl-2 expression. Moreover, MESM reduced DNA fragmentation as well as the infarct size observed by TTC staining. In addition, MESM exhibited an antifibrotic effect by downregulating TGF-1ß expression and reducing collagen deposition in myocardial tissue, as confirmed by Trichrom Masson analysis. The histopathological findings revealed less muscle separation and fewer inflammatory cells in the ISO + MESM-treated rats. Results of the docking simulation indicated that catechin in MESM was inhibitory mainly due to hydrogen bonding interactions with PDI, ACE and TGF-ß1 proteins which could highlight the antithrombotic and antifibrotic capacity of MESM.

Gestational diabetes mellitus induces placental vasculopathies.

Gestational diabetes mellitus (GDM) poses significant long- and short-term risks to both the developing fetus and the mother. GDM can lead to maternal complications during pregnancy and increase the mother's risk of developing type 2 diabetes mellitus and cardiovascular disease later. The present study aimed to evaluate the maternal and fetal vasculopathies in the placenta of Saudi women with GDM. This prospective study examined 84 placentas from full-term pregnant women with no complications other than GDM; 40 placentas were collected from healthy women (controls), and 44 were collected from women diagnosed with GDM. The sampling took place in King Saud University Medical City, Riyadh, between January and August 2019. All placentas were histologically examined according to the Amsterdam Placental Workshop Group (2014, 2015). The results showed that the most common placental changes on the maternal side of the placenta in the GDM group were significant syncytial knots (77%), calcification (70%), villous agglutination (57%), decidual vasculopathy (43%), and retroplacental hemorrhage (34%). Placental infarction was the least common placental change in both groups. On the fetal side, vasculopathies included significant villous fibrinoid necrosis (70.5%), chorangiosis (50%), fibromuscular sclerosis (50%), and villous edema (38.6%). Significant villous fibrinoid necrosis, villous edema, and significant fibromuscular sclerosis were more prevalent in the GDM group. The present study concluded that gestational diabetes mellitus induces histopathological phenotypes in the full-term placenta. Increased decidual vasculopathy, syncytial knots, retroplacental hemorrhage, classification, villous agglutination, chorangiosis, villous edema, villous fibroid necrosis, and fibromuscular sclerosis may indicate GDM in the mother. Such findings in the placenta of a woman who has not been diagnosed with GDM increase the need for GDM examination in future pregnancies.

Ethylbenzene exposure disrupts ovarian function in Wistar rats via altering folliculogenesis and steroidogenesis-related markers and activating autophagy and apoptosis.

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.

Physiological Responses of the Bivalves Mytilus galloprovincialis and Ruditapes decussatus Following Exposure to Phenanthrene: Toxicokinetics, Dynamics and Biomarkers Study.

The aim of the current study was to assess the multifaceted effects of the polycylic aromatic hydrocarbon phenanthrene, mainly used in the colouring, explosive, and pharmaceutical industries, on the physiology of two bivalve species with economic value as seafood, namely, the Mediterranean mussel Mytilus galloprovincyalis and the European clam Ruditapes decussatus. The current study assessed how the phenanthrene affected several biomarkers and biometric endpoints in both bivalves, based on an in vivo experiment in silico approach. The bivalves were exposed during four time slots (i.e., 7, 15, 21, and 28 days) to two concentrations of phenanthrene in water (50 µg/L and 100 µg/L). For the clam R. decussatus, an additional contamination of sediment was applied due their typical benthic lifestyle (50 µg/kg and 100 µg/kg). The phenanthrene significantly reduced the ability of bivalves to tolerate desiccation and their Median Lethal Time, and also inhibited the activity of the enzyme acetylcholinesterase in a time-dependent manner. The activity of catalase indicated that bivalves also experienced oxidative stress during the first 21 days of the experiment. The significant decline in catalase activity observed during the last week of the experiment for the mussel M. galloprovincyalis supported a depletion of enzymes caused by the phenanthrene. The phenanthrene has also toxicokinetic and toxicodynamic properties, as assessed by the in silico approach. Overall, the results obtained suggest that the bivalves Ruditapes decussatus and M. galloprovincyalis can be used as a sentinel species in monitoring studies to assess the environmental impact of phenanthene in marine ecosystems. The significance of our findings is based on the fact that in ecotoxicology, little is known about the chronic effects, the simultaneous use of multiple species as bioindicators, and the interactions molecular modelling.

Long-Term but Not Short-Term Maternal Fasting Reduces Nephron Number and Alters the Glomerular Filtration Barrier in Rat Offspring.

The present study examined the effects of maternal Ramadan-type fasting during selected days in the first, second, or third trimester, or during the entire pregnancy, on the kidney structure of male rat offspring. Pregnant rats were provided with food ad libitum during pregnancy (control group, C), or they were exposed to 16 h of fasting/day for three consecutive days in the middle of the first (FT1), second (FT2), or third trimester (FT3), or during whole pregnancy (FWP). Our results showed that dams in the FWP group demonstrated lower food intake and body weight during gestation. Litter size was unaltered by fasting in all groups; however, litter weight was significantly reduced only in the FWP group. Nephron number was decreased in the FWP group, but it remained unchanged in the other fasting groups. The ultrastructure of the glomerular filtration barrier indicated that the kidneys of offspring of the FWP group demonstrated wider diameters of fenestrations and filtration slits and smaller diameters of basement membranes. This was reflected by a significant increase in proteinuria in FWP only. These results suggest that, unlike with short-term fasting, which seems to be safe, maternal long-term fasting induces structural changes that were non-reversible, and that may contribute to impaired renal function, leading to chronic diseases in later life.

The flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl, as a potential therapeutic agent for breast cancer with a promoting effect on ovarian function.

It is widely known that breast cancer cells eventually develop resistance to hormonal drugs and chemotherapies, which often compromise fertility. This study aimed to investigate the effect of the flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl (KARP), on 1) the viability of MCF-7 breast cancer cells and 2) ovarian function in rats. A dose-dependent decrease in MCF-7 cell survival was observed, and the IC50 value was found to be 48 µg/ml. Cells in the control group or those exposed to increasing concentrations of KARP experienced a similar generation of reactive oxygen species and induction of apoptosis. For the rats, estradiol levels correlated negatively to KARP dosages, although a recovery was obtained at administration of 30 mg/kg per day. Noteworthily, when compared against the control, this dosage led to significant increases in mRNA levels for CYP19, CYP17a, CCND2, GDF9, and INSL3 among the treatment groups, and ER1 and ER2 mRNA levels decreased in a dose-dependent manner. KARP shows great promise as an ideal therapy for breast cancer patients since it induced apoptosis and autophagy in cancerous cells without harming fertility in our animal model. Future investigations on humans are necessary to substantiate these findings and determine its efficacy as a general line of treatment.

Restructuring of a meiobenthic assemblage after sediment contamination with an antibacterial compound: Case study of ciprofloxacin.

A microcosm experiment was conducted to evaluate the impacts of the fluoroquinolone antibiotic ciprofloxacin on meiobenthic taxa abundance, nematode genus structure, and functional trait parameters. Sediment samples were experimentally enriched with four different doses of ciprofloxacin [D1 (50 ppm Dry weight 'DW'), D2 (100 ppm DW), D3 (200 ppm DW), and D4 (500 ppm DW)] and were then compared with non-enriched sediments (controls). After one month of exposure, the data showed that ciprofloxacin had altered the meiofaunal taxa abundance. A change in the structure of nematofaunal genera was observed, particularly with the highest dose (D4), which was characterized by the lowest taxonomic diversity. The SIMPER analysis revealed that the average dissimilarity between nematode communities increased with increasing doses of ciprofloxacin. Two dimensional (2D) non-metric multidimensional scaling (nMDS) plots and relative abundances of functional groups of nematode genus assemblages revealed that all functional trait abundances were affected, particularly with the highest dose. However, only the amphid shape and feeding group functions showed a clear distribution separation between the control and ciprofloxacin treatments. The nMDS second-stage ordination of inter-matrix rank correlations for matrices including genus and functional traits showed that the tail shape was the closest functional trait to the generic distribution. Thus, only the curves of cumulative dominance related to the tail shape mirrored discernibly the sedimentary concentrations in ciprofloxacin.

Syzygium Aromaticum Alleviates Cerium Chloride-Induced Neurotoxic Effect In The Adult Mice.

Previous studies have brought to light the toxic effect of cerium chloride (CeCl3) but very little is known about the oxidative brain injury caused by this metal. Medical plants have a well-recognized role in the management of damage caused by pollutants such as CeCl3. Syzygium aromaticum, a potent natural source of bioactive compounds and rich in secondary metabolites, has a broad range of biological functions. The aim of this study is to investigate the capacity of Syzygium aromaticum ethanol extract (ESA) to improve the adverse effects of CeCl3 in the brain tissue. Adult mice were exposed to CeCl3 (20 mg/kg body weight [BW]), with or without ESA, for 60 days. We investigate mice's behavior, damages of cholinergic system and oxidative stress parameters in mice brain. In the present study, in vitro test confirmed that ESA has antioxidant capacity attributed to the presence of flavonoids, polyphenols, and tannins contents. In vivo study showed that CeCl3 caused brain injuries manifested in memory impairment, increase in acetylcholinesterase activity, oxidative stress biomarkers (lipid, proteins, enzymatic and non-enzymatic antioxidant systems), and histopathological alteration in brain tissue. Addition of ESA repaired memory impairment, decreased acetylcholinesterase activity, restored oxidative state, and prevented histopathological alteration. In conclusion, the experimental results showed the protective effects of ethanol extract of Syzygium aromaticum against cerium-induced brain damage.

Protective effects of Curcuma longa against neurobehavioral and neurochemical damage caused by cerium chloride in mice.

Cerium chloride (CeCl3) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl3, 20 mg/kg BW) along with Curcuma longa extract, administrated by gavage (100 mg/kg BW), into mice for 60 days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl3-treated mice. In addition, CeCl3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl3-treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl3-induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl3-damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl3-induced damage in the brain.

Dynamics of Cytokine-like Activity in the Hyperplasic Ovary of Ex-fissiparous Planarians.

The origin of infertility in the hyperplasic ovary of ex-fissiparous planarians remains poorly understood. In a previous study we demonstrated that a complex process of early autophagy, followed by apoptotic processes, occurs in the hyperplasic ovary of the freshwater planarian Dugesia arabica. The present study aimed to investigate whether the mRNA expression levels of selected mRNA-like genes are altered in the hyperplasic ovary of the ex-fissiparous freshwater planarian D. arabica compared to the normal ovary. Using human cytokine-specific primers including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), we have successfully amplified by real-time polymerase chain reaction some transcripts that could be similar to those amplified in human. The transcript levels of the human-like transcript (IL-1-like and TNF-α-like) were significantly higher, 4.89- and 3.41-fold, respectively, in the hyperplasic ovary compared to the normal ovary (P < 0.05). However, although IL-6-like levels were higher in the hyperplasic ovary than the normal ovary (2.57-fold), this difference was not significant (P > 0.05). Immunohistochemical labeling supported the quantitative real-time PCR, showing that, like their respective mRNA expression levels, IL-1, IL-6, and TNF-α-like proteins are more highly expressed in the hyperplasic ovary than in the normal ovary.

Reproductive strategies, karyology, parasites, and taxonomic status of Dugesia populations from Yemen (Platyhelminthes: Tricladida: Dugesiidae).

We present new data on the distribution, reproductive strategies, karyology, and taxonomic status of populations of freshwater planarians from Yemen. Nine populations were sampled and significant differences in their reproductive strategies and karyology are reported. The present study presents the first fully documented record of a naturally sexual, diploid (2n = 18) population of a Dugesia species in the eastern part of the Afrotropical region. Morphological characters combined with karyological data suggest that these Dugesia populations from Yemen represent a new species, which is herein described as Dugesia arabica Harrath and Sluys, sp. nov. This new species is mainly distinguishable from other Dugesia species that are distributed exclusively in the Mediterranean basin and in the eastern part of the Afrotropical region by the presence of the following features: well-developed and cone-shaped penis papilla, housing an ejaculatory duct that runs ventrally and has a subterminal and ventral opening; a considerably expanded and folded section of the bursal canal at the level of the oviducal openings; absence of a layer of longitudinal muscles on the copulatory bursa and the bursal canal. Specimens from two populations from Yemen were infested with a gregarine Protozoon.