Whirlpool Research Articles

MAEL in human cancers and implications in prognostication and predicting benefit from immunotherapy over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma: a bioinformatic analysis.

Maelstrom (MAEL), a novel cancer/testis-associated gene, may facilitate the initiation and progression of human malignancies, warranting comprehensive investigations. Single-cell and tissue-bulk transcriptomic data demonstrated higher MAEL expression in testis (spermatogonia/spermatocyte), kidney (proximal tubular cell), and brain (neuron/astrocyte), and corresponding cancers, including testicular germ cell tumor, glioma, papillary renal cell carcinoma, and clear cell renal cell carcinoma (ccRCC). Of these cancers, only in ccRCC did MAEL expression exhibit associations with both recurrence-free survival and overall survival. High MAEL expression was associated with an anti-inflammatory tumor immune microenvironment and VEGFR/mTOR activation in ccRCC tissues and high sensitivities to VEGFR/PI3K-AKT-mTOR inhibitors in ccRCC cell lines. Consistent with these, low rather than high MAEL expression indicated remarkable progression-free survival benefits from immune checkpoint inhibitor (ICI)-based immunotherapies over VEGFR/mTOR inhibitors in two large phase III trials (JAVELIN Renal 101 and CheckMate-025). MAEL is a biologically and clinically significant determinant with potential for prognostication after nephrectomy and patient selection for VEGFR/mTOR inhibitors and immunotherapy-based treatments.

Morphine suppresses the immune function of lung cancer by up-regulating MAEL expression

BackgroundPatients with cancer rely on morphine for analgesia, while studies have indicated morphine can induce immunosuppression in cancer. Therefore, investigating the immunosuppressive roles and molecular mechanism of morphine on lung cancer progression is imperative.MethodsLactate dehydrogenase (LDH) release assay was used to determine the cytotoxicity of morphine to lung cancer cells. The percentage of CD4+ and CD8+ T cells was detected by flow cytometry. In addition, Maelstrom (MAEL), Nrf2, and PTEN were determined by western blot and RT-qPCR. Immune factors programmed death-ligand 1 (PD-L1), transforming growth factor (TGF-β), interleukin (IL)-10, and IL-2 were determined by western blot and ELISA assay.ResultsMorphine increased the levels of PD-L1, TGF-β, and IL-10, while decreased IL-2 level. Morphine enhanced MAEL expression in A549 cells and H460 cells. Morphine up-regulated Nrf2 and down-regulated PTEN, and morphine-induced MAEL up-regulation was reversed by PTEN. However, MAEL silencing inhibited the enhanced effects of morphine on cell viability and proliferation of A549 cells. Furthermore, morphine treatment reduced the LDH release and the percentage of CD8+ T cells, and increased the ratio of CD4+/CD8+ T cells and tumor weight. Meanwhile, MAEL silencing reversed the effects of morphine on immune factors (PD-L1, TGF-β, IL-10, and IL-2), the percentage of CD8+ T cells, and the ratio of CD4+/CD8+ T cells.ConclusionMorphine activated MAEL in lung cancer cells by Nrf2/PTEN pathway and regulated the immune factors, thereby promoting tumor immune escape.

MAEL Augments Cancer Stemness Properties and Resistance to Sorafenib in Hepatocellular Carcinoma through the PTGS2/AKT/STAT3 Axis.

Cancer stem cells (CSCs) are responsible for tumorigenesis, therapeutic resistance, and metastasis in hepatocellular cancer (HCC). Cancer/testis antigen Maelstrom (MAEL) is implicated in the formation of CSC phenotypes, while the exact role and underlying mechanism remain unclear. Here, we found the upregulation of MAEL in HCC, with its expression negatively correlated with survival outcome. Functionally, MAEL promoted tumor cell aggressiveness, tumor stem-like potentials, and resistance to sorafenib in HCC cell lines. Transcriptional profiling indicated the dysregulation of stemness in MAEL knockout cells and identified PTGS2 as a critical downstream target transactivated by MAEL. The suppression effect of MAEL knockout in tumor aggressiveness was rescued in PTGS2 overexpression HCC cells. A molecular mechanism study revealed that the upregulation of PTGS2 by MAEL subsequently resulted in IL-8 secretion and the activation of AKT/NF-κB/STAT3 signaling. Collectively, our work identifies MAEL as an important stemness regulation gene in HCC. Targeting MAEL or its downstream molecules may provide a novel possibility for the elimination of CSC to enhance therapeutic efficacy for HCC patients in the future.

Maelstrom promotes tumor metastasis through regulation of FGFR4 and epithelial-mesenchymal transition in epithelial ovarian cancer

BackgroundIncreasing evidence has indicated that Maelstrom (MAEL) plays an oncogenic role in various human carcinomas. However, the exact function and mechanisms by which MAEL acts in epithelial ovarian cancer (EOC) remain unclear.ResultsThis study demonstrated that MAEL was frequently overexpressed in EOC tissues and cell lines. Overexpression of MAEL was positively correlated with the histological grade of tumors, FIGO stage, and pT/pN/pM status (p < 0.05), and it also acted as an independent predictor of poor patient survival (p < 0.001). Ectopic overexpression of MAEL substantially promoted invasiveness/metastasis and induced epithelial-mesenchymal transition (EMT), whereas silencing MAEL by short hairpin RNA effectively inhibited its oncogenic function and attenuated EMT. Further study demonstrated that fibroblast growth factor receptor 4 (FGFR4) was a critical downstream target of MAEL in EOC, and the expression levels of FGFR4 were significantly associated with MAEL. (P < 0.05).ConclusionOur findings suggest that overexpression of MAEL plays a crucial oncogenic role in the development and progression of EOC through the upregulation of FGFR4 and subsequent induction of EMT, and also provide new insights on its potential as a therapeutic target for EOC.

MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma

BackgroundEsophageal cancer is one of the most common malignancies among Iranians and is categorized as adenocarcinoma and squamous cell carcinoma. Various environmental and genetic factors are involved in this malignancy. Despite the recent advances in therapeutic modalities there is still a noticeable mortality rate among such patients which can be related to the late diagnosis. Regarding high ratio of esophageal squamous cell carcinoma (ESCC) in Iran, therefore it is required to assess molecular biology of ESCC to introduce novel diagnostic markers. In present study we assessed the role of Maelstrom (MAEL) cancer testis gene in biology of ESCC among Iranian patients.MethodsForty-five freshly normal and tumor tissues were enrolled to evaluate the levels of MAEL mRNA expression using Real time polymerase chain reaction.ResultsMAEL under and over expressions were observed in 12 (26.7%) and 9 (20%) of patients, respectively. MAEL fold changes were ranged between -4.33 to -1.87 (mean SD: -2.90± 0.24) and 1.92 to 7.72 (mean SD: 3.97± 0.69) in under and over expressed cases, respectively. There was a significant association between stage and MAEL expression in which majority of MAEL over expressed tumors (8/9, 88.9%) were in stage I/II (p<0.001). There was also a significant correlation between MAEL expression and depth of invasion in which tumor with T1/2 had higher levels of MAEL expression compared with T3/4 tumors (p=0.017). Moreover, there were significant correlations between MAEL expression, tumor size (p=0.028), and grade (p=0.003) among male patients.ConclusionsOur data showed that the MAEL was mainly involved in primary stages of tumor progression and it has a declining expression levels toward the advanced stages and higher depth of tumor invasions. Therefore, MAEL can be efficiently introduced as an early detection marker among Iranian ESCC patients.

A pair of whirlpools delicately move an embryo — contact-free

A pair of whirlpools delicately move an embryo — contact-free

Decoding Miracle Food Cures for COVID-19

In early 2020, the mysterious new coronavirus puzzled researchers and panicked millions Scientists had few answers Public health officials were in disanay Few authorities agreed about what, precisely, the coronavirus was, how lethal it could be or how it was spread In this whirlpool of fear and uncertainty, homegrown food cures quickly spread around the world in a global game ot telephone, facilitated by easy forwarding capabilities on Faccbook, and Twitter Miracle food cures promised fast results Rumor had it that boiled garlic water cured the disease Rasam cum;fresh mango, papaya, and durian all were promised to strengthen the immune system Here, Bitar highlights two prominent ones that continue to run amok on the internet: the Israeli secret lemon baking soda tea cure and the Yoniba Nigerian hot pepper stew remedy Both the Israeli tea and Yoniba slew pick up larger cultural currents regarding the special properties of certain foods and flavors -- the sour tang of lemon, the sharp pains of hot peppers and blend them with deep-seated and dangerous ideas about the properties of certain peoples

Intravaginal spermatic cord torsion without whirl pool sign before adolescence

Abstract Spermatic cord torsion in children is a urological emergency that requires operation and fixation within 6 h. Ultrasound sonography allows for the diagnosis of torsion in the early stages; however, some cases are sometimes overlooked and necrotize. While two peaks of onset have been reported (in the neonatal period and adolescence), attention must be paid to prepubertal children as well. Torsion manifests in two ways: as extravaginal torsion (EVT) and intravaginal torsion (IVT). EVT is common in newborns, and IVT is common in adolescents. Bell clapper deformity is thought to be a major cause of IVT. The bell clapper theory describes an anatomical anomaly wherein the testis is freely suspended, leading to its rotation. In EVT, spermatic cord twisting occurs outside of the tunica vaginalis because of a loose connection of the testis to the scrotum in newborns. However, we highlight the fact that IVT can also occur in prepubertal children. A one-year-old and three-year-old boy were admitted to our hospital with testicular pain as the chief complaint. Ultrasonography did not reveal any whirlpool sign. A physical examination showed apparent symptoms of testicular torsion; we therefore performed an emergency operation. We found both boys to be suffering from IVT-type torsion. We corrected the rotation and attempted an ultimately unsuccessful reperfusion. Both testes had bell clapper deformity and were torn in a narrow space. This small space can induce a steep and narrow pitch of torsion far beyond the detectability of ultrasonography. In prepubertal cases, we must pay attention to cases of torsion with no signs of whirlpools after ultrasonography.

Diagnosis and treatment of Roux and Y space hernia after Roux-en-Y gastric bypass surgery for gastric cancer patients: a clinical analysis of 12 cases

Clinical data of 12 patients with gastric cancer, in whom the Roux and Y space hernia developed after gastrectomy with Roux-en-Y anastomosis in our hospital from June 2010 to December 2018, were retrospectively analyzed. The clinical symptoms of patients were abdominal pain, distension and ileus. The main CT findings were torsion of mesentery with whirlpool sign, intestinal obstruction and exudants around the small bowels. During the operation it was found that small bowels herniated into the Roux and Y space in all 12 patients, the necrotic small intestines were resected in 4 patients. Ten patients were recovered, and 2 died. No recurrence was observed in all 10 patients during 3 month-follow up. The postoperative Roux and Y space hernia is a internal hernia and difficult to be diagnosed. The CT scan is valuable for diagnosis of Roux and Y space hernia; the main CT signs were swirled appearance of mesentery and small bowel obstruction. Once diagnosis is made the emergency operation is necessary. Key words: Stomach neoplasms; Hernia, abdominal; Anastomosis, Roux-en-Y

Regions in the Maelstrom of Change

Regions in the Maelstrom of Change

Maelstrom Directs Myeloid-Derived Suppressor Cells to Promote Esophageal Squamous Cell Carcinoma Progression via Activation of the Akt1/RelA/IL8 Signaling Pathway.

Maelstrom (MAEL) is a novel cancer/testis-associated gene, which is not only expressed in the male testicular germ cells among human normal tissues, but is also aberrantly expressed in various cancer tissues. In our study, MAEL was characterized as a tumor-promoting gene and was significantly associated with esophageal squamous cell carcinoma (ESCC) recurrence and unfavorable prognosis. Kaplan-Meier analysis showed that patients with high MAEL expression had a shorter survival time. Functional experiments showed that MAEL promoted tumor cell growth and inhibited cell apoptosis. These results prompted us to investigate the factors affecting the tumorigenicity of MAEL Further experimentation demonstrated that MAEL enhanced the expression of phosphorylated Akt1, with subsequent phosphorylation of nuclear factor kappa B (NF-κB) subunit RelA in tumor cells, and chemoattracted myeloid-derived suppressor cells (MDSCs) by upregulating interleukin-8 (IL8) to accelerate tumor progression in the tumor microenvironment. We also found that TGFβ secreted by MDSCs could upregulate MAEL by inducing Smad2/Smad3 phosphorylation. In summary, this study revealed a mechanism by which MAEL could upregulate IL8 through Akt1/RelA to direct MDSCs homing into the tumor, suggesting that MAEL could be an attractive therapeutic target and a prognostic marker against ESCC. Cancer Immunol Res; 6(10); 1246-59. ©2018 AACR.

HISTORIOGRAPHY &amp; MYTHOLOGY OF BENGAWAN SALA

The aims of this research are: [1]. Describing the historiographic dimension of Bengawan Sala (Solo River), [2]. Describing the mythology alive in the people’s mind along the River Sala, [3]. Formulating revitalization of historiography and mythology of Bengawan Sala which can support the development of tourism in Surakarta. This is a qualitative research making use of primary and secondary sources. Research data were collected by using in-depth interviews, guided group discussions, field observations, and a close reading method (metode simak). Triangulation of data sources was done to ensure the validity of data. Data were analyzed by using the technique of interactive model. The results of the research show that [1]. Historiography of Bengawan Sala is important and singularly valuable when it is viewed from its historical perspective. From its historiographic aspect, Bengawan Sala was a main and urgent channel of transportation before the coming of train, cars and airplanes. [2]. The meanings of mythology around Bengawan Sala, such as Kerek, Lubuk Maya, Bengawan Goa Sentana, Benawi Getas, Lubuk Werpitu, all show the “sacredness” [or “keangkeran”] of Bengawan Sala as a channel for transportation. This mythological story functions to remind all boating people through such areas to be careful because those areas are the place where two different streams from the opposite direction meet each other, or where whirl pools happen. Mythological story of Tinggang depicts the giants which already died, “ambreganggang” shortened as “Tinggang.” People believe that the big wood fossils scattered in the area are the bones of the giants which were already dead, “ambreganggang“ [or “fell down criss-crossing”]. That mythology shows that the lands around Bengawan Sala are fertile. [3]. The exploratory research gives a basic model of “Revitalization Based on the Historiography of Bengawan Sala” (or “Revitalisasi Bengawan Sala Berbasis Kesadaran Sejarah”), that is revitalization of Bengawan Sala through the historiography and mythology development of it.

THE CONTACT OF LANGUAGES

The objective of this paper is to demonstrate that languages in general adopt the monogenetic approach and evolve in a totally independent milieu, and that, however much one fosters the polygenetic approach, they still remain none the less identifable in the light of the characteristics which distinguish and almost isolate them for and as what they are or are supposed to be, whilst at the same time glaringly revealing the crossbreeding elements without which they would not even exist. And this lifelong contact, which exists since the very beginning, should there be any origin that were rigorously traceable and identifable as such, which probably exists even before any origin as such, between languages, this very real contact, although it may seem well-nigh inexistent, this contact which is all the more real as it is unconscious and seems to be perfectly passive, gives, provided we, be it even slightly, develop a conscious and active awareness of it–whence the crucial role of teachers, grammarians, linguists, philosophers and writers– rise both to prospects of hospitality and to risks of hostility, of rejection, due, inter alia, to a sense of fear which, albeit understandable, can only be justifed and explained by the presence or imminence of a cultural siege which it will be precisely up to the teachers, grammarians, linguists, philosophers and writers, though not only to them, to contain, if not to annihilate, so much so that any germ, however unavoidable it may be, of opposition and/or of conflict, may lead to the laying out of an area as much as to the inauguration of an era which will always, upon pain of transmogrifcation into idols, into ideologies, owe it to the atmosphere of renewal, once again the work of teachers, grammarians, linguists, philosophers and writers, but very soon, perhaps thanks to them, the work of one and all, therein prevailing, to keep existing in order that the only outcome resulting from conflict and cooperation, from conflictooperation, may be the mutual enrichment of everybody in a climate of conviviality, the prelude to a perpetual peace amongst human beings, not in spite of their diversity, but because of and thanks to this very diversity. But for this to be possible, to happen, the mere acknowledgement, should it be assumed to be a real and, even, daily occurence, or recognized as such, of contacts between languages, the immediate corollary of which should be the banishment of all forms of nationalism, of all forms of linguistic chauvinism, the dung whence originates the leaven of discord and on which thrive all expressions of bellicosity against the backdrop of a hostile and hateful rejection of any form, of even any semblance of difference, won’t suffice: what is needed is a constant and active reactivation, and activation too, of this contact, of these contacts, which unendingly transform and renew as many languages as possible and all of them if possible, in the whirlpool of a polyphony which, making of them aliens to themselves, brings them closer and closer to one another, for the advent of a new humanity which keeps enriching itself perhaps much more thanks to its differences, than it blossoms through what would constitute a celebration of its fundamental unity.

Reflectance confocal miscroscopy and dermoscopy analysis of a case of connective tissue nevi

Objective To investigate manifestations of connective tissue nevi (CTN) by dermoscopy and reflectance confocal miscroscopy (RCM) , and to analyze its pathological features. Methods According to the course of the disease, skin lesions of a patient with CTN were classified into 2 categories: skin lesions of less than 1-year duration and those of more than 1-year duration, which were observed by dermoscopy and RCM, and analyzed by the combination with histopathological examination. Results Dermoscopy imaging of the CTN lesions of more than 1-year duration showed grey-white maculae with clear boundaries in the center of lesions. There were white network structures, brown globules, red spots and punctiform or comma-shaped blood vessels in the gray-white macula area, and vellus hairs and dermal papillary rings could be seen sometimes. The white macula was evenly surrounded by brown to black pigments, and the boundary was clear. For the lesions of less than 1-year duration, gray-white maculae with clear boundaries were also found in the center of the lesions. Besides, there were a few scattered brown to black pigments, vellus hairs and dermal papillary rings in the gray-white macula area. RCM imaging of the lesions of less than 1-year duration or early skin lesions showed dermal papillae of different sizes and shapes crowded with each other and formed a honeycomb or cobblestone-like structure. The density and brightness of the dermal papilla ring obviously increased, and the refraction of the dermal collagen fiber bundles was also enhanced. Some of the dermal collagen fiber bundles were attached to the dermal papilla or intertwined and arranged in a whirlpool pattern. For the lesions of more than 1-year duration, the refraction of the tissue structure was weakened when the depth in Z-axis direction reached 2 to 3 millimetres due to the thickened epidermis, while the dermal collagen fiber bundles were not obvious and only a few lymphocytes could be seen. Conclusions CTN has particular characteristics in dermoscopy, and there is a definite correspondence among dermoscopy features, histopathological findings and RCM features. RCM is helpful for the diagnosis of lesions of less than 1-year duration. Key words: Dermoscopy; Microscopy, confocal; Pathologic process; Connective tissue nevi

From Armenian Red Sunday to Irish Easter Rising: Incorporating Insurrectionary Politics into the History of the Great War’s Genocidal Turn, 1915-16

The Ottoman Armenians is not in doubt. But historicizing these events within the context of diverse and segmented Armenian responses to the 1914-1918 war has proved more problematic, not least as acknowledging any element of separatist or even insurrectionary intentions might appear to give retrospective legitimacy to the claims that the Ittihadust regime was acting against a genuine security threat. In considering the origins, scope and outcome of the Ottoman-Armenian collision by comparative reference to a synchronous British-Irish dynamic, this essay seeks to more than simply illustrate how peoples across the globe were thrown through the maelstrom of war into unlikely, including sometimes murderous contact with one another. More importantly, its purpose is to probe how for all the singularity of the Medz Yeghern, the Armenian fate might be understood within a broader landscape of emergent European secessionist nationalism and imperial response both during and in the aftermath of the Great War.

Paracrine of human adipose-derived mesenchymal stem cells in three-dimensional culture containing functionized self assembling peptide nanofiber hydrogel

Objective To study the paracrine of human adipose-derived mesenchymal stem cells (ADMSCs) in three-dimensional culture containing functionized self assembling peptide nanofiber hydrogel and the influencing factors. Methods ADMSCs were isolated and extracted. Three kinds of peptides (RADAI-16, RGD, KLT) were prepared and functionized self assembling peptide nanofiber hydrogel was made by mixing RADAI-16, RGD and KLT with a volume ratio of 2∶1∶1. Under AFM, the morphology of RADAI-16, RGD, KLT and functionized self assembling peptide nanofiber hydrogel was observed (n=4). ADMSCs were cultured under the three-dimensional condition containing peptide nanofiber hydrogel. ADMSCs were subjected to in situ three-dimensional cultivation for 1 day, then the concentrations of hepatocyte growth factor (HGF, n=3) and vascular endothelial growth factor (VEGF, n=3) were determined in the supernatatn by enzyme linked immunosorbent assay (ELISA). The cells were extracted in peptide nanofiber hydrogel and the expression of heme oxygenase-1 (HO-1, n=3) was detected by Western blotting. The cultured ADMSCs in hypoxic condition and normal circumstance served as controls. Results ADMSCs showed long spindle shape and grew in a whirlpool shape. The diameter of RADAI-16, RGD, KLT and functionized self assembling peptide nanofiber hydrogel was (17.34±1.82), (15.50±1.41), (13.77±1.18) and (20.26±1.25) nm, respectively. The concentration of HGF under three conditions was (47.31±6.75), (247.86±17.59), and (297.25±17.95) ng/L, respectively, and that of VEGF was (218.30±3.03), (267.13±4.27) and (289.14±3.11) ng/L, respectively. Both HGF and VEGF were paracrined more in condition of functionized self assembling peptide nanofiber hydrogel (P=0.000). Western blotting results showed that the expression of HO-1 in the three-dimensional culture group was about 2 times (P=0.000) higher than that in the ordinary culture group, and was 1.2 times higher than that in the hypoxia culture group (P=0.033). Conclusion The three-dimensional culture mediated by the functionized self assembling peptide nanofiber hydrogel can promote the paracrine of ADMSCs, such as HGF and VEGF, and hypoxia is one of the important elements. Key words: Adipose derived Mesenchymal stem cells; Three-dimensional culture; Functionized self assembling peptide nanofiber hydrogel; Paracrine; Hypoxia

African-Russian family in the maelstrom of conflict. Confession of a countryman

African-Russian family in the maelstrom of conflict. Confession of a countryman

空調用の長距離空気砲・カノン（Kanon）の開発・実証 （第１報）Kanon12-35：到達距離12m・渦輪径35cmφの概要

空調用の長距離空気砲・カノン（Kanon）の開発・実証 （第１報）Kanon12-35：到達距離12m・渦輪径35cmφの概要

Diagnosis and treatment of primary omental torsion: an analysis of 12 cases

Objective To analyze the clinical features, diagnosis and treatment of the primary omental torsion (POT). Method The clinical data of 12 patients with POT admitted to our hospital from May 2010 to May 2015 were retrospectively reviewed. The clinical manifestations, laboratory investigation, medical image, treatment and outcomes of patients were analyzed. Results Twelve cases were all males with median age of 50. The POT was diagnosed during surgical exploration and confirmed pathologically after operation. Right abdominal pain was the main complaint in 11 cases, and pain migration to right lower quadrant in 1 case. In physical examination, the local peritonitis signs were elicited, including right quadrant tenderness and rebound tenderness at same location. All cases had normal temperature except one presenting low fever of 37.5 ℃. White blood cell counts was 12×109/L in one case, and( 4-10)×109/L in other 11 cases. Abdominal solid mass was found in one case by ultrasonic scan, measured 7 cm×5 cm with unclear surrounding boundary. Mesenteric fat opacity and dropsy were shown in 10 cases on CT plain scan, while thickness and effusion of hepatic flexure of colon was found in one case; however, none of them were suggested as POT by these two image study before operation. All patients were diagnosed as localized peritonitis or appendicitis clinically before emergent surgical exploration. The necrotic omentum was resected and all patients recovered smoothly. There were no complications in all cases during one-year follow-up. The CT images were reviewed after operation, which indicated that the mesentery of dropsy and the thickened hepatic flexure of colon should be the imaging signs of omental torsion; and also 9 of 12 cases had whirlpools sign. Conclusion The preoperative diagnosis of POT is difficulty, the typical whirlpools sign of abdominal mass on CT imaging is of highly value in diagnosis. The surgical removal of omental infarction is effective and the prognosis is good. Key words: Torsion, omentum; Fat necrosis; Diagnosis; Therapy

The Waterfall, the Whirlpool, and the Stage "Boundaries of Americanness" in Poe's "A Descent into the Maelstrom"

The Waterfall, the Whirlpool, and the Stage "Boundaries of Americanness" in Poe's "A Descent into the Maelstrom"