Kidney Capsule Research Articles

FIBROMYXOID SARCOMA IN RATTUS NORVEGICUS: CASE REPORT

Myxoid sarcoma comprises malignant tumors of myxoid origin. Low-Grade Fibromyxoid Sarcoma (LGFM) has benign histopathological characteristics, slow growth, but with high metastatic potential. There are at least 25 cases of LGFM in humans, being more common in the deep intramuscular region, mainly in the thigh and trunk, but it has also been described in the retroperitoneum, mesentery and renal capsule. In December 2022, a 2-year-old male Wistar rat (Rattus norvegicus) had difficulty walking and a nodule was noted in the dorsal region of the left pelvic limb, measuring 2.5 cm x 3 cm. In January 2023, amputation was performed and the morphological diagnosis obtained was myxoid sarcoma. In February 2023, formation was observed in the left renal capsule measuring 2cm, growing to 6cm in May 2023, with the same diagnosis as that of the limb. The tutors opted for the surgical removal of the neoformation, however, the animal evolved to death, being referred for necroscopic examination. The case represents the first worldwide case of LGFM in Wistar, the second reported in animals.

FIBROMYXOID SARCOMA IN RATTUS NORVEGICUS: CASE REPORT

Myxoid sarcoma comprises malignant tumors of myxoid origin. Low-Grade Fibromyxoid Sarcoma (LGFM) has benign histopathological characteristics, slow growth, but with high metastatic potential. There are at least 25 cases of LGFM in humans, being more common in the deep intramuscular region, mainly in the thigh and trunk, but it has also been described in the retroperitoneum, mesentery and renal capsule. In December 2022, a 2-year-old male Wistar rat (Rattus norvegicus) had difficulty walking and a nodule was noted in the dorsal region of the left pelvic limb, measuring 2.5 cm x 3 cm. In January 2023, amputation was performed and the morphological diagnosis obtained was myxoid sarcoma. In February 2023, formation was observed in the left renal capsule measuring 2cm, growing to 6cm in May 2023, with the same diagnosis as that of the limb. The tutors opted for the surgical removal of the neoformation, however, the animal evolved to death, being referred for necroscopic examination. The case represents the first worldwide case of LGFM in Wistar, the second reported in animals.

Establishment and evaluation of a modified mouse model of renal subcapsular transplantation of microvolume cells

The renal subcapsular space provides an easily accessible, nutrition-rich pocket that supports engraftment, and as such, is often used as a site for stem and cancer cell transplantation. Renal capsule transplantation requires high technical requirements, the recipient mice have greater surgical damage, the mouse kidney is small and the kidney capsule is fragile, and the operation is easy to fail. The conventional method is not suitable for microvolume cell transplantation to this site in animals with a small kidney, such as mice, due to high risks of cell loss or dislocation or injury to the capsule. In this study, we developed and validated a modified approach for the mouse model of renal subcapsular transplantation of microvolume mouse skeletal stem cells (SSCs). We used a pipette with a refined tip to separate the capsule from the parenchyma. Moreover, we used cells suspended in Matrigel rather than a liquid carrier for transplantation. Using the modified method, we were able to transplant microvolume mouse SSCs as low as 0.2 μL beneath the mouse renal capsule with excellent reproducibility. After 4 weeks of in vivo culture, the implanted mouse SSCs formed grafts on the surface of the parenchyma at the target site of transplantation. Histological staining of the grafts indicated osteogenic, fibrogenic, and lipogenic differentiation. Micro-CT imaging of the grafts revealed bone formation. This modified model could be used to effectively transplant different types of microvolume cells to the renal subcapsular space when the donor cells are difficult to acquire or the recipient mice have a very small size kidney.

A case report on chronic renal disease in a captive wild Leopard Panthera pardus (Mammalia: Carnivora)

A 22-year-old female Common Leopard Panthera pardus at Dhauladhar Nature Park, Gopalpur Zoo was reported to show abnormal behavior in its feeding cubicle during the evening hours and was later found dead. The carcass was presented for necropsy examination at the Department of Pathology, DGCN COVAS, Palampur. Necropsy examination showed enlarged kidneys with completely adhered renal capsule. Lungs and intestine exhibited oedema and hemorrhages, respectively. The histopathological examination found severe necrotic changes with degenerations and fibrosis. Inter-tubular and glomerular collagenous fibrous tissue was confirmed by Masson’s trichrome staining. The animal is speculated to have died primarily due to chronic renal failure with associated pathologies in lungs and intestine.

Depletion of Neural Crest-Derived Cells Leads to Plasma Noradrenaline Decrease and Alters T Cell Development.

The differentiation of neural crest (NC) cells into various cell lineages contributes to the formation of many organs, including the thymus. In this study, we explored the role of NC cells in thymic T cell development. In double-transgenic mice expressing NC-specific Cre and the Cre-driven diphtheria toxin receptor, plasma noradrenaline and adrenaline levels were significantly reduced, as were thymic T cell progenitors, when NC-derived cells were ablated with short-term administration of diphtheria toxin. Additionally, yellow fluorescent protein+ NC-derived mesenchymal cells, perivascular cells, and tyrosine hydroxylase+ sympathetic nerves in the thymus significantly decreased. Furthermore, i.p. administration of 6-hydroxydopamine, a known neurotoxin for noradrenergic neurons, resulted in a significant decrease in thymic tyrosine hydroxylase+ nerves, a phenotype similar to that of depleted NC-derived cells, whereas administration of a noradrenaline precursor for ablating NC-derived cells or sympathetic nerves rarely rescued this phenotype. To clarify the role of NC-derived cells in the adult thymus, we transplanted thymus into the renal capsules of wild-type mice and observed abnormal T cell development in lethally irradiated thymus with ablation of NC-derived cells or sympathetic nerves, suggesting that NC-derived cells inside and outside of the thymus contribute to T cell development. In particular, the ablation of NC-derived mesenchymal cells in the thymus decreases the number of thymocytes and T cell progenitors. Overall, ablation of NC-derived cells, including sympathetic nerves, in the thymus leads to abnormal T cell development in part by lowering plasma noradrenalin levels. This study reveals that NC-derived cells including mesenchymal cells and sympathetic nerves within thymus regulate T cell development.

CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation

BackgroundCDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation.MethodsThe dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig’s epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket.ResultsCDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn’t disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs’ odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs.ConclusionsWe innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Placental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development

Cardiogenic growth factors play important roles in heart development. Placental growth factor (PLGF) has previously been reported to have angiogenic effects; however, its potential role in cardiogenesis has not yet been determined. We analyze single-cell RNA-sequencing data derived from human and primate embryonic hearts and find PLGF shows a biphasic expression pattern, as it is expressed specifically on ISL1+ second heart field progenitors at an earlier stage and on vascular smooth muscle cells (SMCs) and endothelial cells (ECs) at later stages. Using chemically modified mRNAs (modRNAs), we generate a panel of cardiogenic growth factors and test their effects on enhancing cardiomyocyte (CM) and EC induction during different stages of human embryonic stem cell (hESC) differentiations. We discover that only the application of PLGF modRNA at early time points of hESC-CM differentiation can increase both CM and EC production. Conversely, genetic deletion of PLGF reduces generation of CMs, SMCs and ECs in vitro. We also confirm in vivo beneficial effects of PLGF modRNA for development of human heart progenitor-derived cardiac muscle grafts on murine kidney capsules. Further, we identify the previously unrecognized PLGF-related transcriptional networks driven by EOMES and SOX17. These results shed light on the dual cardiomyogenic and vasculogenic effects of PLGF during heart development.

The functional maturity of grafted human pluripotent stem cell derived-islets (hSC-Islets) evaluated by the glycemic set point during blood glucose normalizing process in diabetic mice

Human pluripotent stem cell (hPSCs) derived-pancreatic islets (hSC-islets) are good candidates for cell replacement therapy for patients with diabetes as substitutes for deceased donor-derived islets, because they are pluripotent and have infinite proliferation potential. Grafted hSC-islets ameliorate hyperglycemia in diabetic mice; however, several weeks are needed to normalize the hyperglycemia. These data suggest hSC-islets require maturation, but their maturation process in vivo is not yet fully understood. In this study, we utilized two kinds of streptozotocin (STZ)-induced diabetes model mice by changing the administration timing in order to examine the time course of maturation of hSC-islets and the effects of hyperglycemia on their maturation. We found no hyperglycemia in immune-compromised mice when hSC-islets had been transplanted under their kidney capsules in advance, and STZ was administered 4 weeks after transplantation. Of note, the blood glucose levels of those mice were stably maintained under 100 mg/dl 10 weeks after transplantation; this is lower than the mouse glycemic set point (120–150 mg/dl), suggesting that hSC-islets control blood glucose levels to the human glycemic set point. We confirmed that gene expression of maturation markers of pancreatic beta cells tended to upregulate during 4 weeks after transplantation. Periodical histological analysis revealed that revascularization was observed as early as 1 week after transplantation, but reinnervation in the grafted hSC-islets was not detected at all, even 15 weeks after transplantation. In conclusion, our hSC-islets need at least 4 weeks to mature, and the human glycemic set point is a good index for evaluating ultimate maturity for hSC-islets in vivo.

Comparison of 18F-FDG and 68Ga-FAPI PET/CT in a Rare Renal Leiomyoma.

Renal leiomyoma is a rare benign mesenchymal tumor of the kidney, which mainly originates from the renal capsule or pelvis. We described 18F-FDG and 68Ga-FAPI PET/CT findings in a case of renal leiomyoma. The PET/CT findings showed that the left renal leiomyoma demonstrated intensively increased 68Ga-FAPI uptake, whereas only inhomogeneously slightly increased 18F-FDG uptake. This case illustrates that 68Ga-FAPI PET/CT may be an effective tool for detecting renal leiomyoma.

Unlocking the post-transplant microenvironment for successful islet function and survival.

Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft survivals (5YGS) of 55% and most patients still requiring exogenous insulin after multiple islet infusions. Native islets have a significant non-endocrine component with dense extra-cellular matrix (ECM), important for islet development, cell survival and function. Collagenase isolation necessarily disrupts this complex islet microenvironment, leaving islets devoid of a supporting framework and increasing vulnerability of transplanted islets. Following portal venous transplantation, a liver injury response is potentially induced, which typically results in inflammation and ECM deposition from liver specific myofibroblasts. The impact of this response may have important impact on islet survival and function. A fibroblast response and ECM deposition at the kidney capsule and eye chamber alongside other implantation sites have been shown to be beneficial for survival and function. Investigating the implantation site microenvironment and the interactions of transplanted islets with ECM proteins may reveal therapeutic interventions to improve IT and stem-cell derived beta-cell therapy.

Roles of follicle stimulating hormone and sphingosine 1-phosphate co-administered in the process in mouse ovarian vitrification and transplantation

Some major challenges of ovarian tissue vitrification and transplantation include follicle apoptosis induced by cryopreservation and ischemia-reperfusion injury, as well as ovarian follicle loss during post-transplantation. This research aimed to investigate the protective effects and underlying mechanisms of follicle-stimulating hormone (FSH) and Sphingosine-1-phosphate (S1P) on vitrified and post-transplantation ovaries. Ovaries from 21-day-old mice were cryopreservation by vitrification with 0.3 IU/mL FSH, 2 µM S1P, and 0.3 IU/mL FSH + 2 µM S1P, respectively, for follicle counting and detection of apoptosis-related indicators. The results demonstrated that FSH and S1P co-intervention during the vitrification process could preserve the primordial follicle pool and inhibit follicular atresia by suppressing cell apoptosis. The thawed ovaries were transplanted under the renal capsule of 6–8 week-old ovariectomized mice and removed 24 h or 7 days after transplantation. The results indicated that FSH and S1P co-intervention can inhibit apoptosis and autophagy in ovaries at 24 h after transplantation, and promote follicle survival by up-regulating Cx37 and Cx43 expression, enhanced angiogenesis in transplanted ovaries by promoting VEGF expression, as well as increased the E2 levels to restore ovarian endocrine function at 7 days after transplantation. The hypoxia and ischemia cell model was established by CoCl2 treatment for hypoxia in human granulosa-like tumor cell line (KGN), as well as serum-free culture system was used for ischemia. The results confirmed that ischemia-hypoxia-induced apoptosis in ovarian granulosa cells was reduced by FSH and S1P co-intervention, and granulosa cell autophagy was inhibited by up-regulating the AKT/mTOR signaling pathway. In summary, co-administration of FSH and S1P can maintain ovarian survival during ovarian vitrification and increase follicle survival and angiogenesis after transplantation.

The Possible Protective Effect of Resveratrol on Naphthalene Induced Nephrotoxicity in Adult Male Albino Rat

Abstract Background Resveratrol, a natural polyphenolic compound that is extensively stemmed from grapes, berries, red wine, and peanut skins, is reported with its pharmacological activities against numerous cardiovascular and renal diseases, inflammation, anti-oxidation and cancers. Naphthalene (NA) is a common environmental hazardous contaminant and is abundant in tobacco smoking, in addition to various exposures. Aim of Work the aim of the present work was to study the possible protective effect of Resveratrol on Naphthalene induced nephrotoxicity in adult male albino rat. Materials and Methods 36 Adult male albino rats were assigned randomly into three groups; control group, it was further subdivided into four subgroups (IA received no treatment, IB received Resveratrol 10 mg/kg/day, IC received corn oil 5 mg/kg/day and ID received Propylene glycol), NA group (rats received 200 mg/kg of NA dissolved in 5 ml/kg corn oil daily for four weeks, orally), and Resveratrol protected group (rats received Resveratrol dissolved in propylene glycol at a dose 10 mg/kg followed after 60 min with Naphthalene at a dose 200 mg/kg dissolved in 5 ml/kg corn oil daily for four weeks). At the end of experiment (30 days), rats were euthanized, and kidney specimens were processed into paraffin blocks for light microscopic examination. Morphometric study and statistical analysis were done. Results The present work demonstrated that NA induced several histopathological changes of the kidneys in terms of cortex and medulla. Distorted renal capsule, thickened glomerular basement membrane, scattered small-sized and hypercellular glomeruli with apoptotic cells and narrow Bowman’s spaces. Proximal tubules and the distal tubules showed markedly apoptotic epithelial lining with pyknotic nuclei, partial loss of brush borders, vacuolations and intra-tubular hyaline casts. Congested interstitial blood vessels, peri-vascular edema, massive inflammatory infiltrate and dense collagen distribution. Renal medulla showed collecting tubules with apoptotic epithelial lining with pyknotic nuclei and intratubular hyaline casts. Findings were demonstrated by histomorphometry. Resveratrol protected group showed histopathological findings significantly reduced compared with NA group. Reduced number of scattered small-sized glomeruli with less thickened glomerular basement membrane. The proximal tubules and distal tubules appeared with less apoptotic epithelial lining, fewer pyknotic nuclei and preserved brush borders and interstitium with fair collagen deposition. The medullary regions showed collecting tubules with mostly normal epithelial lining and reduced inflammatory infiltrate. Conclusion The present study demonstrated the deleterious effects of NA on the structure of the kidney. It also suggested the protective role of Resveratrol against the nephrotoxicity.

Human A2-CAR T Cells Reject HLA-A2 + Human Islets Transplanted Into Mice Without Inducing Graft-versus-host Disease.

Type 1 diabetes is an autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta-cells. Islet transplantation is an effective therapy, but its success is limited by islet quality and availability along with the need for immunosuppression. New approaches include the use of stem cell-derived insulin-producing cells and immunomodulatory therapies, but a limitation is the paucity of reproducible animal models in which interactions between human immune cells and insulin-producing cells can be studied without the complication of xenogeneic graft-versus-host disease (xGVHD). We expressed an HLA-A2-specific chimeric antigen receptor (A2-CAR) in human CD4 + and CD8 + T cells and tested their ability to reject HLA-A2 + islets transplanted under the kidney capsule or anterior chamber of the eye of immunodeficient mice. T-cell engraftment, islet function, and xGVHD were assessed longitudinally. The speed and consistency of A2-CAR T-cell-mediated islet rejection varied depending on the number of A2-CAR T cells and the absence/presence of coinjected peripheral blood mononuclear cells (PBMCs). When <3 million A2-CAR T cells were injected, coinjection of PBMCs accelerated islet rejection but also induced xGVHD. In the absence of PBMCs, injection of 3 million A2-CAR T cells caused synchronous rejection of A2 + human islets within 1 wk and without xGVHD for 12 wk. Injection of A2-CAR T cells can be used to study rejection of human insulin-producing cells without the complication of xGVHD. The rapidity and synchrony of rejection will facilitate in vivo screening of new therapies designed to improve the success of islet-replacement therapies.

Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i−/−) arrested tooth root formation, indicated by truncated Hertwig’s epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i−/− mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i−/− mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i−/− odontoblasts. Through treating pulp precursor cells with Atp6i−/− or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i−/− OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i−/− mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.

The mTOR Inhibitor Rapamycin Counteracts Follicle Activation Induced by Ovarian Cryopreservation in Murine Transplantation Models.

Background and Objectives: Ovarian tissue cryopreservation followed by autotransplantation (OTCTP) is currently the only fertility preservation option for prepubertal patients. Once in remission, the autotransplantation of frozen/thawed tissue is performed when patients want to conceive. A major issue of the procedure is follicular loss directly after grafting mainly due to follicle activation. To improve follicular survival during the OTCTP procedure, we inhibited the mTOR pathway involved in follicle activation using rapamycin, an mTOR inhibitor. Next, we compared two different in vivo models of transplantation: the recently described non-invasive heterotopic transplantation model between the skin layers of the ears, and the more conventional and invasive transplantation under the kidney capsule. Materials and Methods: To study the effects of adding rapamycin during cryopreservation, 4-week-old C57BL/6 mouse ovaries, either fresh, slow-frozen, or slow-frozen with rapamycin, were autotransplanted under the kidney capsule of mice and recovered three weeks later for immunohistochemical (IHC) analysis. To compare the ear with the kidney capsule transplantation model, fresh 4-week-old C57BL/6 mouse ovaries were autotransplanted to either site, followed by an injection of either LY294002, a PI3K inhibitor, vehicle control, or neither, and these were recovered three weeks later for IHC analysis. Results: Rapamycin counteracts cryopreservation-induced follicle proliferation, as well as AKT and mTOR pathway activation, in ovaries autotransplanted for three weeks under the kidney capsule of mice. Analyses of follicle proliferation, mTOR activation, and the effects of LY294002 treatment were similar in transplanted ovaries using either the ear or kidney capsule transplantation model. Conclusions: By adding rapamycin during the OTCTP procedure, we were able to transiently maintain primordial follicles in a quiescent state. This is a promising method for improving the longevity of the ovarian graft. Furthermore, both the ear and kidney capsule transplantation models were suitable for investigating follicle activation and proliferation and pharmacological strategies.

Time- and Gender-Dependent Alterations in Mice during the Aging Process.

Compared to young people and adults, there are differences in the ability of elderly people to resist diseases or injuries, with some noticeable features being gender-dependent. However, gender differences in age-related viscera alterations are not clear. To evaluate a potential possibility of gender differences during the natural aging process, we used three age groups to investigate the impact on spleens, kidneys, and adrenal glands. The immunofluorescence results showed that male-specific p21 proteins were concentrated in the renal tubule epithelial cells of the kidney. Histological staining revealed an increase in the frequencies of fat vacuoles located in the renal tubule epithelial cells of the cortex, under the renal capsule in the kidneys of male mice with age. In female mice, we found that the width of the globular zone in the adrenal gland cortex was unchanged with age. On the contrary, the male displayed a reduction in width. Compared to females, the content of epinephrine in adrenal gland tissue according to ELISA analysis was higher in adults, and a greater decline was observed in aged males particularly. These data confirmed the age-dependent differences between female and male mice; therefore, gender should be considered one of the major factors for personalized treatment in clinical diagnosis and treatment.

Recurrence of composite hemangioendothelioma of the kidney after surgical resection

Composite hemangioendothelioma is an extremely rare form of kidney tumor. The tumor mainly occurs in the extremities, head and neck; internal organs involvement is rarely reported. Patient, 61-year-old male, was admitted to the urology department for a left kidney tumor, which was found accidentally during an ultrasound examination. Magnetic resonance imaging showed an irregularly shaped tumor measuring 5.0 × 6.0 × 4.0 cm and located in the lower pole of the left kidney. The tumor was surgically removed with resection of the capsule of the kidney lower pole. Immunohistochemical study revealed diffuse bright expression of CD31 (clone JC70A), CD34 (clone QBEnd 10), ERG (clone ER111), FLI-1 (clone MRQ-1) in tumor cells. The index of proliferative activity Ki-67 (clone SP6) was 40 %. The morphological picture and immunophenotype of the tumor correspond to composite hemangioendothelioma of the retroperitoneal space. Magnetic resonance imaging of the retroperitoneal space on follow-up visit in 9 months visualized a tumor of the left kidney measuring 8.3 × 8.4 × 7.8 cm. Radical nephrectomy was performed. Pathology examination showed that tumor tissue was mainly represented by solid fields of the spindle cell component. In samples of the border between the tumor and fatty pararenal tissue, tumor invasion was observed up to the adjacent striated muscles, tumor growth into the tissue of the kidney gate was also found. Taking into account the morphological picture and the earlier immunohistochemical study, the removed tumor corresponds to composite hemangioendothelioma.Composite hemangioendothelioma is a tumor of low malignant potential. It is extremely rare for this tumor to affect the kidney. At the same time, in the described case, the tumor was initially located in the retroperitoneal space, with involvement of the kidney capsule, and was assessed as a benign lesion. After 9 months, there was a recurrence of the tumor localized in the kidney with damage to the elements of the renal sinus, retroperitoneal tissue, and lumbar muscles. In this case, the tumor has significant malignant potential.

Anomalous origin of the left suprarenal, inferior phrenic arteries and left ovarian artery in a human cadaver.

This report addresses three variants identified within a female cadaver. Specifically, these were an anomalous origin of the right suprarenal artery, an abnormal bilateral ovarian vein branch, and a arterial tortuosity of the left ovarian artery. Indeed, the cadaver evinced abnormal origins in the case of the middle suprarenal artery (MSA), right inferior phrenic artery (IPA), and the renal capsule artery (emanating from the right renal artery). The MSA and IPA shared a common trunk with the inferior suprarenal artery. It was additionally observed that the right ovarian vein anastomoses the branches from the right kidney posterior inferior along with those to the renal fat capsule. Abnormal origin was evident in the case of the left ovarian artery, and arterial tortuosity was apparent in the lower region of the vessels. This report addresses both the clinical import of these variations and their likely causes. In the subdiaphragmatic region, surgical success and prognosis may be impacted by such anomalies; accordingly surgeons must be aware of anatomical variants of the ovarian and suprarenal arteries.

Investigating the protective effects ofElaeagnus angustifoliafruit extract on hematological parameters and damage of different tissues of male mice exposed to graphene oxide nanoparticles

AbstractThe aim of this study is to investigate the protective effects ofElaeagnus angustifoliafruit extract (EAFE) on hematology, biochemical parameters, liver enzymes and damage of different tissues of male mice exposed to graphene oxide nanoparticles (GO NPs). In this research, 48 mice were divided into six groups. Hematology parameters including red blood cells (RBC), white blood cells (WBC), hematocrit (Ht), and hemoglobin (Hb), biochemical parameters such as cholesterol, triglyceride, glucose, protein, albumin, creatinine and bilirubin, liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and histological damage of liver, kidney, lung and testis of mice were investigated. The results show that GO NPs in both concentrations (30 and 60 mg/kg/bw) decrease the number of RBC compared to the control group (p &lt; 0.05). EAFE has no effect on RBC count while EAFE in combination with both concentrations of 30 and 60 mg/kg/bw GO NPs significantly (p &lt; 0.05) improves the RBC count of mice. Also, the results show that EAFE improves the number of WBC, Ht, Hb, and biochemical parameters of mice exposed to different concentrations of GO NPs. A series of morphological changes were observed in the RBC of rats exposed to 60 mg/kg/bw GO NPs, including Dacrocyte, Poikilocyte and Schistocyte, which EAFE can improve the morphological changes caused in RBC. A series of histological damages such as degeneration and dilatation in the central vein in liver tissue, thickening and inflammatory cell infiltration in the renal capsule, peribronchiolar inflammatory cell infiltration and congestion in peribronchiolar blood vessels in lung tissue and decrease in the height of the germinal epithelium and a decrease in the population of spermatozoid cells in spermatogenic cells were observed in the testis of mice exposed to 60 mg/kg/bw GO NPs. The results show that EAFE can improve the damage caused by GO NPs in the liver, kidney and lung tissues, while it has no effect on the damage in the mice testis tissue. Therefore, GO NPs cause damage in the blood and different tissues of mice, and the use of EAFE can be effective in improving these damages.

Greb1 Transiently Accelerates Pancreatic β-Cell Proliferation in Diabetic Mice Exposed to Estradiol

Decrease of pancreatic β cells leads to diabetes. In an inducible cAMP early suppressor (ICER-Iγ) transgenic mouse model of severe type 2 diabetes with reduced insulin production and depleted β cells, supplementation with high concentrations of 17β-estradiol (E2) markedly enhances β-cell proliferation and normalizes glucose levels. The current study explored the underlying mechanisms leading to a dynamic increase of β cells and pathologic changes in diabetic mice exposed to E2. Gene expression profiling of pancreatic islets of 6-month-old ICER-transgenic mice recovering from diabetes due to elevated E2 levels identified growth regulation by estrogen in breast cancer 1 (Greb1) as a gene significantly up-regulated during the recovery phase. To substantiate this, β-cell-specific Greb1-deficient mice were generated, and Greb1 was shown to be essential for recovery of depleted β cells in diabetic mice. Graft growth and glucose lowering were observed in 50 islets with increased Greb1 expression transplanted adjacent to E2 pellets beneath the kidney capsule of streptozotocin-induced diabetic mice. Greb1 expression due to a drastic increase in exogenous or endogenous E2 was transient and closely correlated with changes in E2-related and some cell cycle-related genes. These findings provide new insights into invivo proliferation of deficient β cells and suggest the possibility of new therapeutic approaches targeting pancreatic β cells that could revolutionize the concept of diabetes treatment, which has been considered difficult to cure completely.