Placental Form Research Articles

Genotoxic and Anti-Genotoxic Assessments of Fermented Houttuynia cordata Thunb. Leaf Ethanolic Extract and Its Anti-Cancer Effect in a Dual-Organ Carcinogenesis Model of Colon and Liver in Rats.

The incidence of multiple-organ cancers has recently increased due to simultaneous exposure to various environmental carcinogens. Houttuynia cordata Thunb. (H. cordata) is recognized for its many health benefits, including its anti-cancer properties. The fermentation of its leaves has been shown to significantly enhance the bioflavonoid content and its bioactivities. This study aimed to evaluate the effectiveness of fermented H.cordata leaf (FHCL) extracts against combined carcinogens and investigate the underlying mechanisms. The crude ethanolic extract of FHCL was partitioned to obtain hexane- (HEX), dichloromethane- (DCM), ethyl acetate- (ETAC), butanol- (nBA), and residue fractions. The crude ethanolic extract (200-250 μg/mL) and the DCM fraction (50 μg/mL) significantly reduced NO production in RAW264.7 macrophages. In addition, the crude extract and the DCM and ETAC fractions showed anti-genotoxicity against aflatoxin B1 and 2-amino-3,4-dimethylimidazo [4,5-f]quinoline (MeIQ) in Salmonella typhimurium assays (S9+). Despite demonstrating genotoxicity in the Salmonella mutation assay (with and without S9 activation), oral administration of the crude extract at 500 mg/kg of body weight (bw) for 40 days in rats did not induce micronucleated hepatocytes, indicating that the extract is non-genotoxic in vivo. Moreover, the crude extract significantly decreased Phase I but increased Phase II xenobiotic-metabolizing enzyme activities in the rats. Next, the anti-cancer effects of FHCL were evaluated in a dual-organ carcinogenesis model of the colon and liver in rats induced by 1,2-dimethylhydrazine (DMH) and diethylnitrosamine (DEN), respectively. The crude extract significantly reduced not only the number and size of glutathione S-transferase placental form positive foci in the liver (at doses of 100 and 500 mg/kg bw) but also the number of aberrant crypt foci in rat colons (at 500 mg/kg bw). Furthermore, FHCL significantly reduced the expression of proliferating cell nuclear antigen (PCNA) in the colon (at 100 and 500 mg/kg bw) and liver (at 500 mg/kg bw) of the treated rats. In conclusion, FHCL exhibits significant preventive properties against colon and liver cancers in this dual-organ carcinogenesis model. Its mechanisms of action may involve anti-inflammatory effects, the prevention of genotoxicity, the modulation of xenobiotic-metabolizing enzymes, and the inhibition of cancer cell proliferation. These findings support the use of FHCL as a natural supplement for preventing cancer.

Thai Fermented Soybean (Thua-Nao) Prevents Early Stages of Colorectal Carcinogenesis Induced by Diethylnitrosamine and 1,2-Dimethylhydrazine Through Modulations of Cell Proliferation and Gut Microbiota in Rats.

Thua-nao is a traditional fermented soybean product widely consumed in the northern areas of Thailand. There has been little research on the biological activity of Thua-nao, particularly its anticancer properties. The objective of this study was to examine the cancer chemopreventive effects of dried Thua-nao on liver and colorectal carcinogenesis induced by carcinogens in rats. Rats were injected with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) to induce preneoplastic lesions. Rats orally received dried Thua-nao for 13 weeks. The preneoplastic lesions, including glutathione S-transferase placental form (GST-P)-positive foci and aberrant crypt foci (ACF), were evaluated in the liver and colon, respectively. The cancer chemopreventive mechanisms of dried Thua-nao on liver and colorectal carcinogenesis were examined. Dried Thua-nao administration suppressed colorectal aberrant crypt foci. Moreover, dried Thua-nao reduced proliferation cell nuclear antigen (PCNA)-positive cells in the colon. Interestingly, dried Thua-nao modulated the gut microbiota in DEN- and DMH-induced rats. Isoflavones, including genistein and daidzein, represent promising chemopreventive agents in dried Thua-nao. In conclusion, these results highlight the cancer chemopreventive effect of dried Thua-nao in DEN and DMH-induced colorectal carcinogenesis through cell proliferation reduction and gut microbiota modulation.

Cancer Chemopreventive Effect of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone on Diethylnitrosamine-Induced Early Stages of Hepatocarcinogenesis in Rats.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.

Who was the real sabertooth predator: Thylacosmilus or Thylacoleo?

Sabertoothed mammalian predators, all now extinct, were almost exclusively feloid carnivorans (Eutheria, Placentalia): here a couple of extinct metatherian predators are considered in comparison with the placental sabertooths. Thylacosmilus (the "marsupial sabertooth") and Thylacoleo (the "marsupial lion") were both relatively large (puma-sized) carnivores of the Plio-Pleistocene in the Southern Hemisphere (Argentina and Australia, respectively). Both carnivores have captured the public imagination, especially as predators that were somehow analogous to northern placental forms. But a more detailed consideration of their morphology shows that neither can be simply analogized with its supposed placental counterpart. While Thylacosmilus did indeed have saber-like canines, many aspects of its anatomy show that it could not have killed prey in the manner proposed for the sabertoothed felids such as Smilodon. Rather than being an active predator, it may have been a specialized scavenger, using the hypertrophied canines to open carcasses, and perhaps deployed a large tongue to extract the innards. Thylacoleo lacked canines, and its supposedly "caniniform" incisors could not have acted like a felid's canines. Nevertheless, while its mode of dispatching its prey remains a subject for debate, it was clearly a powerful predator, likely to be capable of bringing down prey bigger than itself while hunting alone. In that regard, it may have filled the ecomorphological role proposed for placental sabertooths, and so despite the lack of canines can be nominated as the true "marsupial sabertooth" out of the two extinct taxa.

Perioperative Outcomes, Risks and Complications Associated with Placenta Previa and Placenta Accreta Spectrum Revisited From an Anesthesiology Perspective

Purpose: Placenta previa (PP) and placenta accreta spectrum are forms of abnormal placentation, and they are associated with significant perinatal morbidity and mortality. The objective of the present study was to juxtapose the baseline data, clinical features, perioperative outcomes, risks, and complications associated with PP and placenta accreta spectrum. 
 Materials and Methods: This retrospective study was performed using data extracted from the medical files of a total of 300 patients diagnosed with PP (Group I, n=237) and placenta accreta spectrum (Group II, n=63). The information gathered for every patient consisted of baseline descriptives, perinatal data and need for intraoperative or postoperative blood transfusion, pre- and postoperative serum levels of hemoglobin, fibrinogen and C-reactive protein, need and duration for intensive care unit stay, whether hemodialysis and mechanical ventilation were employed. 
 Results: The body-mass index was remarkably higher in Group II (p=0.002). There was no statistically significant difference between two groups concerning baseline descriptive data and perinatal, perioperative, and postoperative variables. 
 Conclusion: Results of the present study demonstrated that despite adequate planning and optimal management strategies; the likelihood of significant morbidity and mortality associated with PP and placenta accrete spectrum is still remarkable. Early and close monitoring with careful preparation is momentous for antepartum and intrapartum management. Additional research is essential to determine the predisposing factors as well as ideal methods of diagnosis, treatment, and prevention.

Decidual cells and decidualization in the carnivoran endotheliochorial placenta.

Decidualization is considered a distinctive feature of eutherian pregnancy, and has appeared during evolution along with the development of invasive forms of placentation, as the endotheliochorial placenta. Although decidualization is not massive in carnivores, as it is in most species developing hemochorial placentas, isolated or grouped cells regarded as decidual have been documented and characterized, mainly in bitches and queens. For the majority of the remaining species of the order, data in the bibliography are fragmentary. In this article, general morphological aspects of decidual stromal cells (DSCs), their time of appearance and lasting, data about the expression of cytoskeletal proteins and molecules considered as markers of decidualization were reviewed. From the data reviewed, it follows that carnivoran DSCs take part either in the secretion of progesterone, prostaglandins, relaxin, among other substances, or at least in the signaling pathways triggered by them. Beyond their physiological roles, some of those molecules are already being used, or are yet under study, for the non-invasive endocrine monitoring and reproductive control of domestic and wild carnivores. Only insulin-like growth factor binding protein 1, among the main decidual markers, has been undoubtedly demonstrated in both species. Laminin, on the contrary, was found only in feline DSCs, and prolactin was preliminary reported in dogs and cats. Prolactin receptor, on the other hand, was found in both species. While canine DSCs are the only placental cell type expressing the nuclear progesterone receptor (PGR), that receptor has not been demonstrated neither in feline DSCs, nor in any other cell in the queen placenta, although the use of PGR blockers leads to abortion. Against this background, and from the data gathered so far, it is unquestionable that DSCs in carnivorans do play a pivotal role in placental development and health. The knowledge about placental physiology is critical for medical care and breeding management, primarily in domestic carnivores; it is also absolutely crucial for a conservation approach in the management of endangered carnivore species.

Cancer chemopreventive potential of cooked glutinous purple rice on the early stages of hepatocarcinogenesis in rats.

Cancer prevention using dietary phytochemicals holds great potential, particularly in the alternative treatment of liver cancer. Our previous study found that the methanol extract of cooked purple rice performed various biological functions including antioxidant, anti-inflammatory, and antimutagenic activities in in vitro assays. This study aimed to evaluate the chemopreventive effects of cooked glutinous purple rice extract (CRE) obtained from routine rice cooking method on diethylnitrosamine (DEN)-induced hepatic preneoplastic lesions in rats, along with its inhibitory mechanisms. CRE containing γ-oryzanols and high amounts of polyphenolic compounds, particularly cyanidin-3-glucoside, was fed to rats over a period 15 weeks. Additionally, injections of triple DEN at a concentration of 100 mg/kg BW were administered to rats once a week during the second, third, and fourth weeks of the experiment. The results revealed that CRE did not induce the formation of glutathione S-transferase placental form (GST-P) positive foci as a precancerous lesion during rat hepatocarcinogenesis, indicating non-carcinogenicity. Furthermore, CRE significantly reduced the number and size of GST-P positive foci in DEN-initiated rats. It also modulated microenvironment homeostasis by reducing the number of PCNA positive hepatocytes and by enhancing the number of apoptotic positive hepatocytes in the livers of DEN-initiated rats. Using RT-PCR analysis, CRE decreased the mRNA expression of some proinflammatory mediators, including interleukin-6, interleukin-1 beta, inducible nitric oxide synthase and cyclooxygenase 2, by attenuating the expression of cyclin E, the proliferation marker, while also inducing the expression of the apoptotic gene, Bcl2 associated X. The inhibitory mechanism at the early stages of hepatocarcinogenesis of CRE may be involved with the attenuation of cell proliferation, the enhancement of apoptosis, and the modulation of the proinflammatory system. Anthocyanins, flavonoids, and γ-oryzanol represent a group of promising chemopreventive agents in cooked glutinous purple rice extract. The outcomes of this study can provide an improved understanding of the potential role of the phytochemicals contained in cooked purple glutinous rice with regard to cancer alleviation.

Enriched Riceberry Bran Oil Exerts Chemopreventive Properties through Anti-Inflammation and Alteration of Gut Microbiota in Carcinogen-Induced Liver and Colon Carcinogenesis in Rats.

Simple SummaryRice bran oil is gaining popularity around the world due to its ability to improve lipid profiles. Recent in vitro studies have shown that the active compounds in colored rice bran oil exhibited anti-cancer properties in various cell lines. However, there has been a limited number of animal studies focusing on the anti-carcinogenic action of rice bran oil. In this study, Riceberry bran oil (RBBO) extracted from the bran of a Thai-pigmented rice variety, namely Riceberry, was investigated for its inhibitory mechanism on the early stages of liver and colorectal carcinogenesis using the dual carcinogens-induced rat model. RBBO was able to inhibit the biomarkers of rat liver cancer and colon cancer by forcing cells to undergo apoptosis, reducing inflammation, and changing the profiles of bacteria and their metabolites. These findings suggest that RBBO could be a promising source of high-value chemopreventive agents in terms of both cancer prevention and treatment.Riceberry has recently been acknowledged for its beneficial pharmacological effects. Riceberry bran oil (RBBO) exhibited anti-proliferation activity in various cancer cell lines. However, animal studies of RBBO on anti-carcinogenicity and its molecular inhibitory mechanism have been limited. This study purposed to investigate the chemopreventive effects of RBBO on the carcinogen-induced liver and colorectal carcinogenesis in rats. Rats were injected with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) and further orally administered with RBBO equivalent to 100 mg/kg body weight of γ-oryzanol 5 days/week for 10 weeks. RBBO administration suppressed preneoplastic lesions including hepatic glutathione S-transferase placental form positive foci and colorectal aberrant crypt foci. Accordingly, RBBO induced hepatocellular and colorectal cell apoptosis and reduced pro-inflammatory cytokine expression. Interestingly, RBBO effectively promoted the alteration of gut microbiota in DEN- and DMH-induced rats, as has been shown in the elevated Firmicutes/Bacteroidetes ratio. This outcome was consistent with an increase in butyrate in the feces of carcinogen-induced rats. The increase in butyrate reflects the chemopreventive properties of RBBO through the mechanisms of its anti-inflammatory properties and cell apoptosis induction in preneoplastic cells. This would indicate that RBBO containing γ-oryzanol, phytosterols, and tocols holds significant potential in the prevention of cancer.

IMMUNOHISTOCHEMICAL EVALUATION OF VIMENTIN IN ENDOTHELIUM OF VESSELS OF UTERO-PLACENTAL BED DURING THE IRON DEFICIENCY ANEMIA IN PREGNANCY

Iron deficiency anemia in pregnant women (IDA) is a pressing problem in modernobstetrics, the frequency of which reaches 85 %. In previous studies, we have found thatduring gestation against a background of IDA placental bed of the uterus morphologicallyhas signs of gestational immaturity, the severity of which correlates with the degree ofanemia. Vimentin is the main intermediate protein of cytoskeleton, which is expressed inendothelial and other cells of the mesenchyme. Vimentin mediates tissue processes suchas cell adhesion, migration, invasion, angiogenesis and vasculogenesis. In order to verifythe previously obtained data on morphometric parameters of hemodynamics in placentalbed of the uterus depending on the degree of IDA and elucidation of morphogenesis ofutero- placental form of placental insufficiency due to gestational immaturity, we usedthe method of immunohistochemical visualization of vimentin in endothelium of variousvessels of utero- placental area.Purpose of the work – to determine the features of immune expression of vimentin in thevascular endothelium of the uterine- placental region in iron deficiency anemia in theapect of chronic placental insufficiency at 37-40 weeks of gestation.Materials and methods. 140 biopsies of utero- placental bed were morphologically studied,obtained during caesarean section, observations of physiological pregnancy and gestationagainst a background of IDA I-III degree in terms of chronic placental insufficiency. Theconcentration of hemoglobin in the blood of the pregnant woman was the criterion of IDAseverity degree according to medical records. According to A.P. Milivanov classificationof chronic placental insufficiency (1999), the uterine- placental form of it was diagnosedby Doppler examination followed by detection of morphological equivalents.Results. An increase of vimentin immunoexpression indices as a marker of preservationof a part of leiomyocytes at incomplete gestational transformation, which correlates withthe degree of gestational immaturity of uteroplacental area (UPA) and anemia and is themost essential at pregnancy with clinical signs of UPA against a background of IDA, wasmarked in all cases of pregnancy against a background of IDA in the walls of the spiralarteries. For endothelial cells of the venous vessels, this trend of increasing optical densityof staining for vimentin is characteristic only for IDA I and II degrees, while against thebackground of IDA III degree with signs of placental isufficiency indices of vimentinimmunoexpression are lower than those in physiological pregnancy. In the endothelialcells of the vessels of the microcirculatory tract there is a moderate decrease in the opticaldensity of staining for vimentin in cases of IDA I and II degrees without signs of placentalisufficiency, but in observations with UPA against a background of anemia II degreea slight increase was noted. At IDA III degree the level of vimentin immunoimaging is1,5 times lower in comparison with physiological pregnancy. These features are probablydue to the attenuation of the processes of angiogenesis and vasculogenesis in the uterineplacental area in IDA II-III degrees, as well as the increase in dyscirculatory phenomenaand damage the vascular endothelium.Conclusions. During pregnancy against the background of iron deficiency anemia, theplacental bed morphologically has signs of gestational immaturity. The revealed featuresof vimentin immunoexpression in endothelial cells of different types of vessels give thepossibility to consider that morphological preconditions are formed for hypoperfusionof the uterine- placental area and the development of disturbances of the venous outflowfrom the placental bed of the uterus as predictors of uteroplacental form of chronicplacental insufficiency.

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis

Our previous study demonstrated that purple rice bran extract (PRBE) could inhibit diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Protocatechuic acid (PCA) is the major phenolic acid contained in the PRBE. Therefore, this study aimed to determine whether PCA is an anticarcinogenic compound in purple rice extract. Rats were intraperitoneally injected with DEN to induce glutathione S-transferase placental form (GST-P)-positive foci. Rats were fed with PRBE at 500 mg kg−1 body weight or PCA at 4 mg kg−1 body weight for 5 and 15 weeks. PCA administration attenuated DEN-induced hepatic GST-P positive foci to a degree similar to PRBE. The molecular mechanisms of PCA in the initiation stage were correlated with reduced activity of cytochrome P450 reductase and induction of glutathione S-transferase. In addition, PCA also downregulated the expression of TNF-α and IL-1β genes in rat liver. These genes are associated with the inhibition of inflammation. In the promotion stage, PCA suppressed cell proliferation correlated with the downregulation of Cyclin D1 expression. Moreover, it also induced apoptosis, indicated by increased expression of P53 and Bad genes, and decreased the expression of the anti-apoptotic Bcl-xl in DEN-initiated rats. These findings suggest that PCA is an active compound in the anticarcinogenic action of purple rice bran.

Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats.

Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione S-transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD50 value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.

Malaria Parasite Plasmodium falciparum Proteins on the Surface of Infected Erythrocytes as Targets for Novel Drug Discovery.

Specific adhesion (sequestration) of Plasmodium falciparum parasite-infected erythrocytes (IEs) in deep vascular beds can cause severe complications resulting in death. This review describes our work on the discovery, characterization, and optimization of novel inhibitors that specifically prevent adhesion of IEs to the host vasculature during severe malaria, especially its placental and cerebral forms. The main idea of using anti-adhesion drugs in severe malaria is to release sequestered parasites (or prevent additional sequestration) as quickly as possible. This may significantly improve the outcomes for patients with severe malaria by decreasing local and systemic inflammation associated with the disease and reestablishing the microvascular blood flow. To identify anti-malarial adhesion-inhibiting molecules, we have developed a high-throughput (HT) screening approach and found a number of promising leads that can be further developed into anti-adhesion drugs providing an efficient adjunct therapy against severe forms of malaria.

Lack of hepatocarcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane, 3-hydroxy-2-naphthoic acid, and acetoacetanilide in a medium-term rat liver bioassay.

The carcinogenicity of 2,2'-[1,2-ethanediylbis(oxymethylene)]bis-oxirane (ethylene glycol diglycidyl ether; EGDE), 3-hydroxy-2-naphthoic acid (HNA), and acetoacetanilide (AAA) was investigated using a medium-term rat liver bioassay for an occupational safety assessment. F344 male rats were administered a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body weight (bw)/day) and then starting 2 weeks later, they received EGDE at 6, 20, and 60 mg/kg bw/day, HNA at 20, 60, and 200 mg/kg bw/day, or AAA at 60, 200, and 600 mg/kg bw/day by oral gavage for 6 weeks. The animals in the positive control group received phenobarbital sodium solution (PB, 25 mg/kg bw/day) by oral gavage and those in the negative control group received a vehicle (water/corn oil) during the administration period of test substances in this model. All animals were subjected to two-thirds partial hepatectomy at week 3 and euthanized at week 8. Neither the number nor the area of hepatocellular foci positive for glutathione S-transferase placental form (GST-P) increased in any of the EGDE, HNA, or AAA treated groups. However, the number and area of GST-P-positive foci significantly increased in the positive control group treated with PB. The results indicate that EGDE, HNA, and AAA lack hepatocarcinogenicity in rats.

Searching for placenta percreta: a prospective cohort and systematic review of case reports

Placenta percreta is described as the most severe grade of placenta accreta spectrum and accounts for a quarter of all cases of placenta accreta spectrum reported in the literature. We investigated the hypothesis that placenta percreta, which has been described clinically as placental tissue invading through the full thickness of the uterus, is a heterogeneous category with most cases owing to primary or secondary uterine abnormality rather than an abnormally invasive form of placentation. We have evaluated the agreement between the intraoperative findings using the International Federation of Gynecology and Obstetrics classification with the postoperative histopathology diagnosis in a prospective cohort of 101 consecutive singleton pregnancies presenting with a low-lying placenta or placenta previa, a history of at least 1 prior cesarean delivery and ultrasound signs suggestive of placenta accreta spectrum. Furthermore, a systematic literature review of case reports of placenta percreta, which included histopathologic findings and gross images, was performed. Samples for histologic examination were available in 80 of 101 cases of the cohort, which were managed by hysterectomy or partial myometrial resection. Microscopic examination showed evidence of placenta accreta spectrum in 65 cases (creta, 9; increta, 56). Of 101 cases included in the cohort, 44 (43.5%) and 54 (53.5%) were graded as percreta by observer A and observer B, respectively. There was a moderate agreement between observers. Of note, 11 of 36 cases that showed no evidence of abnormal placental attachment at delivery and/or microscopic examination were classified as percreta by both observers. The systematic literature review identified 41 case reports of placenta percreta with microscopic images and presenting symptomatology, suggesting that most cases were the consequence of a uterine rupture. The microscopic descriptions were heterogeneous, and all descriptions demonstrated histology of placenta creta rather than percreta. Our study supported the concept that placenta accreta is not an invasive disorder of placentation but the consequence of postoperative surgical remodeling or a preexisting uterine pathology and found no histologic evidence supporting the existence of a condition where the villous tissue penetrates the entire uterine wall, including the serosa and beyond.

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Physiopathology of late-onset fetal growth restriction.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its potential for genetic determination. FGR can have several causes, including genetic syndromes, chromosomal diseases, and infections; however, a vast majority of cases are probably attributed to impaired uterine and placental circulation. The relationships between abnormal placental development and FGR are complex, and studies are generally few, presenting confounding factors. Damage to the uteroplacental circulation associated with vasculogenesis and villus angiogenesis dysfunction are the main factors involved in subsequent FGR. The main receptors involved in FGR include hypoxia-inducible factor (HIF 1, 2, and 3), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), vascular endothelial growth factor C (VEGF-C), soluble Flt-1, soluble endoglin (Seng), angiopoietin-1 and -2 (Ang-1 and Ang-2), tyrosine kinase receptor 1 (Flt-1), tyrosine kinase receptor 2 (Flt-2), vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3, kinase domain receptor (KDR), and vascular endothelial growth factor receptor A (VEGFR-A). Furthermore, failure in trophoblastic invasion and remodeling of spiral arteries has been associated with FGR owing to poor placental perfusion. There are several possible causes for poor remodeling of spiral arteries, which probably vary on a case-to-case basis. Changes in the placental form, macroscopic and microscopic vascular lesions, inflammation, and genetic changes are also related to FGR. Based on gestational age at diagnosis, FGR can be classified as early- (˂32 weeks) and late-onset (≥32 weeks). Moreover, there exist several theories regarding possible pathophysiological differences between early- and late-onset FGR, with some postulating that it the same disease but at different stages or severity. Another hypothesis suggests that the change in the trophoblastic invasion of spiral arteries would be milder. In this article, we address the main mechanisms described in the pathophysiology of FGR and, later, the specific findings in late-onset FGR.

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Protective Role of Vanillic Acid against Diethylnitrosamine- and 1,2-Dimethylhydrazine-Induced Hepatocarcinogenesis in Rats.

This study aimed to evaluate the cancer chemopreventive activity of vanillic acid (VA) in diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon carcinogenesis in rats. VA did not induce the formation of hepatic glutathione S-transferase placental form (GST-P) positive foci and colonic aberrant crypt foci, demonstrating no carcinogenic activity. VA (75 mg kg−1 body weight) could significantly reduce the number and areas of hepatic GST-P positive foci when administered before carcinogen injections, but no such effect was seen when it was administered after carcinogen injection. No protection was seen in the colon when VA was treated before or after carcinogen injection. Immunohistochemical studies demonstrated the decreased expression of proliferating cell nuclear antigen and the induction of apoptosis. Mechanistic studies showed that VA significantly induced the expression of GSTA-5 and Nrf-2 genes, which are associated with the detoxification system. Likewise, the antiproliferative effect was noticed by the reduction of Cyclin D1 expression. The apoptotic activity may be due to the upregulation of Caspase-3 and Bad levels and downregulation of the Bcl-2 level. These data suggest that VA exhibited significant protection against diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis, which might be related to the induction of the detoxifying enzyme, the reduction of proliferation and the induction of apoptosis.

Low-polar extract from seed of Cleistocalyx nervosum var. paniala modulates initiation and promotion stages of chemically-induced carcinogenesis in rats

BackgroundCleistocalyx nervosum var. paniala is a local fruit mainly cultivated in the north of Thailand. Our previous study has reported that the methanol extract of C. nervosum seed presented antimutagenicity in a Salmonella mutation assay. The present study focused on the effect of a low-polar extract of C. nervosum seed on the early stages of diethylnitrosamine (DEN)- and dimethylhydrazine (DMH)-induced carcinogenesis in rats. MethodsDried C. nervosum seed powder was extracted using dichloromethane. To study its effect on the initiation stage of carcinogenesis of rats, they were fed with various doses of C. nervosum seed extract (CSE) for 21 days. DEN injection was used to initiate hepatocarcinogenesis and partial hepatectomy was performed to amplify mutated hepatocytes resulting in micronucleated hepatocyte formation. To study the role of CSE on the promotion stage, rats were injected with DEN and DMH to induce preneoplastic lesions and the numbers of glutathione S-transferase placental form (GST-P) positive foci in the liver and aberrant crypt foci (ACF) in the colon were measured. This was followed by CSE administration for 10 weeks. The inhibitory mechanisms of CSE on initiation and promotion stages, including xenobiotic metabolism, cell proliferation and apoptosis, were investigated. ResultsThe total phenolic content in CSE was 80.34 ± 2.29 mg gallic acid equivalents (GAE) per g of extract and 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone was found to be a major flavonoid. The main terpenoids in CSE were β-selinene, α-selinene, γ-selinene and o-cymene while 24(Z)-methyl-25-homocholesterol was a major phytosterol. CSE significantly decreased the number of micronucleated hepatocytes in DEN-initiated rats and enhanced the activities of hepatic glutathione S-transferase and UDP-glucuronyltransferase. Furthermore, the formation of preneoplastic lesions in the liver and colon was statistically reduced by CSE. CSE also diminished cell proliferation in the liver and colon indicated by the number of PCNA positive cells. However, CSE did not alter the numbers of apoptotic hepatocytes and colonocytes in DEN- and DMH-initiated rats. ConclusionsThe dichloromethane extract of C. nervosum seed demonstrated chemopreventive effects on chemically-induced carcinogenesis in both initiation and promotion stages in rats. The inhibitory mechanism might be involved in the modulation of hepatic detoxifying enzymes and suppression of hepatocyte and colonocyte proliferation.