Bad Gene Research Articles

Investigation of the Apoptotic and Antimetastatic Effects of Nano-Niosomes Containing the Plant Extract Anabasis setifera on HeLa: In Vitro Cervical Cancer Study.

The present study focuses on the preparation of niosomes containing an extract of Anabasis setifera and evaluates their efficacy in inhibiting the growth and proliferation of HeLa cells. Thin-layer hydration technique was used to prepare niosomes/extract nanoparticles (NPs). The physicochemical properties of the synthesized NPs were confirmed by scanning electron microscope (SEM), dynamic light scattering (DLS), zeta potential analysis, and FTIR. The cytotoxicity of the free extract, free niosome, and NPs was investigated by MTT (3-(4, 5-diMethylThiazol-2-yl)-2,5-diphenylTetrazolium bromide) assay. For this purpose, solutions of the three mentioned agents were prepared and diluted in 400, 200, 100, 50, 25, 12.5, and 6.25µg/mL concentrations and incubated for 24, 48, and 72h. After calculating the IC50 concentration and treating the cells with this concentration, real-time polymerase chain reaction (PCR) (to measure changes in the expression of apoptosis and metastasis genes), flow cytometry (to determine the amount of early and late induced apoptosis), and cell cycle test (to determine the stopping stage of the cancer cell division cycle) were performed. Moreover, the scratch test (the ability to inhibit cell metastasis after treatment) was used to evaluate cell migration. The MTT assay results showed that 72h of treatment with NPs has the greatest effect on the death of cancer cells. Real-time PCR showed that the expression of the Bad gene increased dramatically and the expression of the BCL-XL, integrin alpha 5 (ITGA5), and zinc finger E-box-binding homeobox 1 (ZEB-1) genes decreased significantly. The flow cytometry results showed that 48.64% of HeLa cells underwent apoptosis after treatment with synthesized NPs. The scratch test results showed that cancer cell metastasis stopped after treatment with NPs. The research demonstrates the significant potential of plant extract-loaded niosomes, as highly efficient drug carriers for cancer therapy.

Inhibition of mitochondria induces apoptosis and reduces telomere length and activity in acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is a highly lethal hematological malignancy in adults and children. Abnormal proliferation of leukemia stem cells (LSC) with CD34+ and CD38- phenotypes are the main clinical features of AML. Patients with AML face drug resistance and treatment failure due to a default in stem and progenitor cells. Therefore, defining LSC properties is necessary for targeting leukemia-initiating cells. Mitochondrial mass and activity increase in AML initiating cells compared with normal stem cells. This idea has offered the inhibition of the mitochondrial translation machinery to reduce the number of leukemia-initiating cells in patients with AML Tigecycline is an FDA-approved microbial antibiotic that inhibits oxidative phosphorylation in mitochondria, resulting in the suppression of leukemia cell proliferation with little toxicity to normal cells. Thus, the present study was conducted to evaluate whether LSC is influenced by mitochondrial inhibition. We measured the IC50 of tigecycline in KG-1a AML cell lines. KG-1a AML cell lines were separated into CD34+ and CD34- cells by MACS. In the following, these cells were treated with 20 µM (IC50) tigecycline. The expression of Annexin/PI, Caspase 3, apoptotic genes (BCL2, BCLX, BAX, BAD, and P53) and proteins (P53, BAX, BCL2 and Caspase 9) was evaluated in CD34+ , CD34- and KG-1a AML cells. In addition, the telomere length and expression of hTERT were evaluated in this study. The results indicated that BCl2 (gene and protein) and BCLX gene dramatically decreased. In addition, BAD, BAX, and P53 gene and protein expression significantly increased in CD34+ AML cells compared to CD34- AML cells. The results also suggested that tigecycline induced intrinsic (Cleaved-caspase 9/Pro-Caspase 9 ratio) and p53-mediated apoptosis. Furthermore, hTERT gene expression and telomere length decreased in the tigecycline-treated groups. Taken together, our findings indicate that inhibition of mitochondrial activity with tigecycline can induce apoptosis in cancer stem cells and can be used as a novel method for cancer therapy.

Effects of hypoxia and reoxygenation on oxidative stress, histological structure, and apoptosis in a new hypoxia-tolerant variety of blunt snout bream (Megalobrama amblycephala)

A new hypoxia-tolerant variety of blunt snout bream was obtained by successive breeding of the wild population, which markedly improved hypoxia tolerance. In this study, the hypoxia-tolerant variety was exposed to hypoxia (2.0 mg O2·L−1) for 4, 7 days. The contents of blood biochemical indicators including the number of red blood cells (RBC), total cholesterol (T-CHO), total protein (TP), triglyceride (TG), glucose (GLU), and lactic acid (LD) increased significantly (P < 0.05) under hypoxia. The glycogen content in the liver and muscle decreased significantly (P < 0.05) and the LD content in the brain, muscle and liver increased significantly (P < 0.05) under hypoxia. The levels of oxidative stress-related indicators i.e., superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T-AOC) also changed significantly (P < 0.05) in the heart, liver, and intestine of the new variety under hypoxia. Additionally, hypoxia has caused injuries to the heart, liver, and intestine, but it shows amazing repair ability during reoxygenation. The apoptotic cells and apoptosis rate in the heart, liver, and intestine increased under hypoxia. Under hypoxia, the expression of the B-cell lymphomas 2 (Bcl-2) gene in the heart, liver, and intestine was significantly (P < 0.05) down-regulated, while the expression of the BCL2-associated agonist of cell death (Bad) gene was significantly (P < 0.05) up-regulated. These results are of great significance for enriching the basic data of blunt snout bream new variety in response to hypoxia and promoting the healthy development of its culture industry.

Acute Hypoxia Stress-Induced Apoptosis in Gill of Japanese Flounder (Paralichthys olivaceus) by Modulating the Epas1/Bad Pathway.

The physiological responses and molecular mechanisms of apoptosis in Japanese flounder under hypoxic stress remain unclear. In the present study, we performed acute hypoxia stress on Japanese flounder (2.39 ± 0.84 mg/L) and detected gills responses in histomorphology and molecular mechanisms. The results showed that the volume of the interlamellar cell mass decreased and the gill lamellae prolonged, indicating the expansion of the respiratory surface area. Additionally, the fluorescence signal of apoptosis increased under hypoxic stress. In addition, the expression of two genes (EPAS1 and Bad) related to apoptosis increased about four-fold and two-fold, respectively, at 6 h of hypoxia. Meanwhile, the result of the dual-luciferase reporter assay showed that EPAS1 is a transcription factor, which could regulate (p &lt; 0.05) the expression of the Bad gene, and we identified the binding site of EPAS1 was the AATGGAAAC sequence located near -766. DNA methylation assay showed that hypoxia affected the methylation status of CpG islands of EPAS1 and Bad genes. All results indicated that hypoxia could activate the EPAS1/Bad signal pathway to induce gill apoptosis of Japanese flounder. Our study provides new light on understanding the molecular mechanism of hypoxia-induced apoptosis in Japanese flounder.

Screening of proliferation related lncRNAs in leukemia cell lines by lentivirus shRNA library combined with second-generation sequencing

Long non-coding RNA (lncRNA) has become an important regulator of many cellular processes, including cell proliferation. Although studies have shown that a variety of lncRNAs play an important role in the occurrence and development of hematopoietic malignancies, a more comprehensive and unbiased method to study the function of lncRNAs in leukemia cell lines is lacking. Here, we used short hairpin RNA (shRNA) library combined with high-throughput sequencing to screen lncRNAs that may affect the proliferation of leukemia cell lines, and identified lncRNA C20orf204-203 among 74 candidate lncRNAs in this study. Further experiments showed that C20orf204-203 was localized in the cytoplasm in both K562 and THP-1 cell lines. C20orf204-203 knockdown decreased the proliferation of K562 and THP-1 cell lines accompanied with the increased proportion of early apoptotic cells. We observed the increased mRNA level of BAD gene while decreased protein level of TP53 and BCL2. The expression of Caspase 3 decreased and Caspase 3-cleaved protein increased in THP-1 cell line. However, their changes were inconsistent in the two cell lines. Our experimental results showed that knockdown of lncRNA C20orf204-203 in leukemia cell lines affected cell proliferation although the mechanism of action in different cell lines may differ. Importantly, our research demonstrated the feasibility of using shRNA library combined with high-throughput sequencing to study the role of lncRNA in leukemia cell lines on a large scale.

Outer Stars

Outer Stars Kirsten Sundberg Lunstrum (bio) That evening when he does not come home, Clara makes dinner for their daughter and carries on with their routines as if nothing is wrong. Outside, the city has not yet gone quiet. People are still returning from their day of work. The street below their fifth-story window is still bustling with the traffic of passing cars and bicycles. If there is anything markedly different about the scene—unfamiliar or unsettling—she's not sure what it might be, except maybe his absence. She feels it like a breath held—the waiting, a small pause in her body's rhythms, a pressure at the center of her chest that she knows will release the moment he walks through the door. "R U OK?" she texts him. "XO," he writes. The whole night passes. "Why isn't Dad home?" Moira asks over breakfast the next morning. The news is on the television, a woman in a red dress reporting before a digital background image of a sunny blue sky. Out the window, the real sky is the color of cooked and cooling egg whites, soft and opaque. The reporter echoes what has been said and said over the last twenty-four hours, words like particulate and aerosols that might once have simply been terms but which are now panic invoking. They predict rain, which will clear it. Stay tuned for the full forecast. Clara turns it off. Moira is six. She looks like Clara, tawny hair and gray-brown eyes. Sometimes looking at her daughter is for Clara like seeing herself in a warped mirror. It's not the resemblance so much as a shadow of doubt or distrust—a feeling she's known all her life, and which her daughter, with all the love and attention she's been given as the only child of parents who desperately wanted her, certainly has no reason to feel. It's a feeling Clara would like to have spared her girl. Crack in a glass, snag in a cloth, knot of anxiety under the surface of every day. Little voice in her center whispering [End Page 161] nothing lasts. Can you inherit uncertainty? It pains Clara to think she's passed it on, like a bad gene, this propensity for finding the dark hole of any moment. She sets a bowl of cereal in front of Moira, the swim of bluish milk floating a sparkle of cinnamon and sugar crystals, and watches the girl stir before eating. With the first bite the concern on the child's face dissipates like clouds thinning. Moira tips the cereal bowl, drinks the sweet milk, and smiles, temporarily sated. She is elfin in the way of all not-yetadolescent children—long limbed and bigheaded. Cute and fragile and still in need of mother-love. Clara kisses her forehead, clears away the bowl. Moira gallops across the room, clambers up onto the couch, and cranes over to look out the window. "When Dad gets home, we're going to build a model of the ship from Outer Stars," Moira says. "Really?" Clara answers from the kitchen, just feet away. This apartment is small, efficient, but always enough for them. "Sounds like you two have a plan." Clara says it like it will be only hours. Like a sure thing. "We do have a plan," the child says. "We'll play Outer Stars, then we'll repticate it." Moira grins, lifts her eyebrows—a new gesture, another mirror of one of Clara's own. "Replicate it?" Clara asks, hoping Moira will correct herself. "We're building it exactly. Exactly." Outer Stars is a video game her husband and Moira play together on the weekends while Clara reads a book in the other room or goes out alone to walk where she will not be spoken to or needed. In the game, you—the player, but also the protagonist—have been sent into space following an undefined apocalyptic event that has made Earth uninhabitable. Space is your new landscape, in all its endless darkness, and your challenge is to make that darkness home. The darkness is not, however, vacant, nor even actually dark...

Tastes Like War by Grace M. Cho

Reviewed by: Tastes Like War by Grace M. Cho Sunhay You (bio) Tastes Like War, by Grace M. Cho. New York: Feminist Press, 2021, 296 pp. ISBN: 9781952177941. An “unintended sequel” to Haunting the Korean Diaspora, Grace Cho’s memoir, Tastes Like War, engages in a sociological mode of storytelling (6). Her voice is familiar, evoking the autoethnographic portions of her first book: an “experimental writing voice . . . intended to show the mixing up of fact and fiction, of self and other, so neither a discreet narrator nor a clear storyline is always [End Page 143] present” (203). True to her commitments to unraveling the limits of a discreet authorial subject, Cho weaves together Korean recipes, psychological texts, history, personal anecdotes, and dreams to uncover the tacit knowledge that lies in the wake of her mother’s schizophrenia. The memoir peels away at the insights of her first book, revealing another US imperial structure of shame and secrecy besides the military bride: mental disability. In the opening prologue, Cho claims that she was raised by at least three different mothers. The mother of her early childhood is a charismatic entrepreneur who sells foraged wild blackberries while supporting other racial minorities. Cho’s teenage years mark the onset of her mother’s schizophrenia, when she becomes a “prisoner to the voices that told her to stop doing the things she used to do” (3). In her thirties, Cho begins to observe her mother's vivacious qualities return while teaching Cho how to cook Korean food. The breaks in these three mothers organize the breaks between parts 2 to 4 of the memoir, the prologue and part 1 offering the sociological framework to her storytelling. As Cho cites throughout the first section, theories on the relationship between mental disability and structures of racial-sexual violence are relatively new. While research on schizophrenia from the 1970s and 80s explains the condition as “the result of a bad gene,” more recent studies suggest that schizophrenia is symptomatic of a social disease as much as a biological anomaly (4). Referring to T. M. Lurhmann’s 2016 study Our Most Troubling Madness: Studies in Schizophrenia, Cho explains that five of the six risk factors associated with schizophrenia apply to her mother: low socioeconomic status, childhood adversity, physical or sexual trauma, immigration, and “being a person of color in a white neighborhood” (56). Indeed, besides narratives of her mother’s passage to the United States as a military bride, many of Cho’s early recollections of her mother take place in Chehalis, Washington. She notes that the city is known for having hosted a regional meeting of approximately seventy thousand members of the KKK in 1924, a legacy of white supremacy that continues today. Cho’s mother grows especially paranoid about being a target of “the John Birch Society, a radical right-wing organization founded in 1958 and named after an American who had been killed by the Chinese at the end of World War II” (136). Through these details,Cho demonstrates how her mother’s experiences of racial-sexual violence undergird developments in her schizophrenic paranoia, which would later confine her to the home, the curtains drawn and cabinets closed on a dwindling supply of food. In part 3, Cho delves into the structural obstacles she faced as a teenager trying to help her mother in the absence of such a nuanced understanding of schizophrenia. A doctor at the local mental health center told her that if her mother was in danger of hurting someone, the police could force her mother [End Page 144] to seek treatment. Given her age and inability to convince her mother of her schizophrenia, Cho resorts to calling the police after aggravating one of her mother’s schizophrenic episodes. This event plants a seed of mistrust that casts a shadow over Cho’s future attempts to care for her mother. These careful and honest observations present a wide-spanning cognitive map of institutional structures, histories, and cultural forces that have impacted her mother's mental health as a military bride. Anecdotes about the healing power of food interrupt the more daunting stories of racial-sexual violence that give shape to her mother...

The Key Target and Molecular Mechanism of the Volatile Component of Scutellaria baicalensis Georgi in Acute Lung Injury Based on Network Pharmacology.

Ethnopharmacological relevance: Scutellaria baicalensis georgi is one of the most widely studied TCMs; its effects in ALI have been studied in a large number of experiments, and the efficacy of volatile oil from TCM remains to be studied. Aim: The volatile component of Scutellaria baicalensis georgi was selected to act on the key target of acute lung injury and was preliminarily studied for its specific molecular mechanism. Methods: The volatile active substances of Scutellaria baicalensis georgi were extracted by GC–MS, and the active ingredients related with the occurrence and development of acute lung injury were searched and matched by the TCMSP database. The pharmacologic data and analysis platform of TCM were used to retrieve and screen for the volatile active components and the possible therapeutic targets of Scutellaria baicalensis georgi. In addition, acute lung injury was searched in the disease target database to identify the corresponding disease target proteins, thereby establishing a protein–protein interaction network. Finally, the effects of wogonin on the apoptotic and inflammatory factors in the acute lung injury cell model were analyzed experimentally. Results: We identified 100 candidate targets and successfully constructed a complex target network. The targets identified by the above gene enrichment analysis played important roles in the autoimmune disease cell cycle apoptosis and related signaling pathways. The KEGG pathway analysis showed that most of the target genes were involved in the inflammatory response regulation of the TRP, PI3K-Akt, and IL-17 signaling pathways. The participation of wogonin in the specific regulatory pathways of PI3K-Akt signaling and IL-17 signaling was verified through experiments. In the lung-injured cell model, the results showed that wogonin inhibited the apoptosis of injured lung cells by inhibiting the expression of BAD gene and the activation of cleaved caspase-3 gene while increasing Bcl-2 expression. In addition, wogonin inhibited the expression of the abovementioned inflammatory factors and further inhibited the inflammatory response in the lung injury cells. Conclusion: The results of pharmacological network analysis can predict and explain the regulation mechanism of multi-target and multi-pathway of TCM components. This study identified the potential target and important pathway of wogonin in regulating acute lung injury. At the same time, the accuracy of network pharmacological prediction is also preliminarily verified by molecular biology experiment.

Survivin Regulates Bad Gene Expression by Binding to Its Promoter and Modulates Cell Cycle and Apoptosis in Esophageal Carcinoma Cell.

Esophageal cancer (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. As an antiapoptotic and a proapoptotic protein, respectively, survivin and Bad play an important role in carcinogenesis of the most human cancers including EC. However, the regulatory relationships between them remain unclear. We sought to investigate the effects of survivin knockdown and overexpression on the expression of Bad gene, cell cycle progression, and apoptosis of esophageal carcinoma cell. The mRNA expression levels of survivin and Bad were determined in EC tissue samples. The knockdown and overexpression experiments were performed in ECA109 and KYSE450 cells via transfection with survivin overexpression and shRNA plasmids. A Bad overexpression experiment was conducted to confirm the biological effect on knockdown of survivin via modulating Bad expression. RT-qPCR and Western blot analysis were used to detect mRNA and protein expression, respectively. Cell cycle and apoptosis were analyzed by flow cytometry. The chromatin immunoprecipitation (ChIP) was conducted to determine the binding sites of survivin on the promoter of Bad gene. By analyzing the mRNA expression of survivin and Bad in 40 ESCC patient specimens, we found that the positive expression rate of survivin in tumor tissues (88%, 35/40) was remarkably high, compared with the distal nontumor tissues (48%, 19/40, p < 0.01). On the other hand, the positive expression rate of Bad in tumor tissues (70%, 28/40) was remarkably low, compared with the distal nontumor tissues (95%, 38/40, p < 0.01). Overexpression of survivin decreases Bad mRNA and protein expression and promotes transformation of cell cycle to S phase. Conversely, knockdown of survivin increases Bad mRNA and protein expression and induces cell cycle arrest and apoptosis. Bad overexpression inducing apoptosis of esophageal carcinoma cell shows the similar apoptotic effect with survivin knockdown. ChIP assays indicate that survivin directly binds to the Bad promoter region, diminishing the transcriptional activity of Bad. In conclusion, the result suggested that survivin regulates Bad gene expression by binding to its promoter and modulates cell cycle and apoptosis in esophageal carcinoma cell.

Identification of a secreted superoxide dismutase (SOD) from Nocardia seriolae which induces apoptosis in fathead minnow (FHM) cells.

Fish nocardiosis is a chronic systemic granulomatous disease, and Nocardia seriolae is the main pathogen. The pathogenesis and virulence factors of N. seriolae are not fully understood. Secreted superoxide dismutase (SOD) may be a virulence factor found by a comparative bioinformatics analysis of the whole genome sequence of N. seriolae and thevirulence factor database (VFDB). In order to determine the subcellular localization and study the preliminary function of SOD from N. seriolae (NsSOD), gene cloning, secreted protein identification, subcellular localization in fish cells, and apoptosis detection of NsSOD were carried out in this study. Subcellular localization research revealed that NsSOD-GFP fusion proteins were evenly distributed in the cytoplasm. Furthermore, apoptotic bodies were observed in the transfected FHM cells by the overexpression of protein NsSOD. Then, assays of mitochondrial membrane potential (ΔΨm) value, caspase-3 activity and apoptosis-related genes (Bax, Bid, Bad and Bcl-2) mRNA expression were conducted. The results showed that ΔΨm was decreased, and caspase-3 was significantly activated. The mRNA expression of the Bad gene showed significant up-regulated expression at 24 h.p.t., while Bid and Bax genes showed significant up-regulated expression at 72 and 96 h.p.t. and anti-apoptotic gene (Bcl-2) was down-regulated in NsSOD overexpressed cells. Taken together, the results indicated that the protein NsSOD might be involved in apoptosis regulation. This study may lay the foundations for further studies on the function of NsSOD and promote the understanding of the virulence factors and the pathogenic mechanisms of N. seriolae.

The Impact of Ang-(1-9) and Ang-(3-7) on the Biological Properties of Prostate Cancer Cells by Modulation of Inflammatory and Steroidogenesis Pathway Genes.

The local renin–angiotensin system (RAS) plays an important role in the pathophysiology of the prostate, including cancer development and progression. The Ang-(1-9) and Ang-(3-7) are the less known active peptides of RAS. This study examines the influence of these two peptide hormones on the metabolic activity, proliferation and migration of prostate cancer cells. Significant changes in MTT dye reduction were observed depending on the type of angiotensin and its concentration as well as time of incubation. Ang-(1-9) did not regulate the 2D cell division of either prostate cancer lines however, it reduced the size of LNCaP colonies formed in soft agar, maybe through down-regulation of the HIF1a gene. Ang-(3-7) increased the number of PC3 cells in the S phase and improved anchorage-independent growth as well as mobility. In this case, a significant increase in MKI67, BIRC5, and CDH-1 gene expression was also observed as well as all members of the NF-kB family. Furthermore, we speculate that this peptide can repress the proliferation of LNCaP cells by NOS3-mediated G2/M cell cycle arrest. No changes in expression of BIRC5 and BCL2/BAX ratio were observed but a decrease mRNA proapoptotic BAD gene was seen. In the both lines, Ang-(3-7) improved ROCK1 gene expression however, increased VEGF and NOS3 mRNA was only seen in the PC3 or LNCaP cells, respectively. Interestingly, it appears that Ang-(1-9) and Ang-(3-7) can modulate the level of steroidogenic enzymes responsible for converting cholesterol to testosterone in both prostate cancer lines. Furthermore, in PC3 cells, Ang-(1-9) upregulated AR expression while Ang-(3-7) upregulated the expression of both estrogen receptor genes. Ang-(1-9) and Ang-(3-7) can impact on biological properties of prostate cancer cells by modulating inflammatory and steroidogenesis pathway genes, among others.

Ghazal : [inline-graphic 01i], and: Calligraphies XI, and: Makdisi Street Calligraphies

Ghazal : [inline-graphic 01i], and: Calligraphies XI, and: Makdisi Street Calligraphies Marilyn Hacker (bio) Ghazal : Halab, Qamishli, Isdoud, for Ovid, once Rome—in the heartof exile, one name remains home in the heart. There are some stones and a small pile of ash in the desert.There is the silence beneath a magnificent dome in the heart. I look out at a three-quarter moon after three weeks’ confinementthat daily inflames a desire to roam in the heart. Not every old lady—but some—looking frail in the marketor too stout on the bus, has an insolent môme in the heart. The bad gene for cancer I probably got from my father.My blood pressure rises from which chromosome in the heart? Such palpitations, and all of them augur departure,throbbing beneath the unmarked aerodrome in the heart. What’s the djinn in my mind makes me want what I shouldn’t?I created that golem, invited that gnome in the heart. Silenced, the call to , the first bell of matins,in my cloister still start up the same metronome in the heart. your faces look out on all four chambers.If I am not honest with you, there’s no poem in the heart. [End Page 36] Calligraphies XI Fayza said to me“During the day, I’m happy,lonely when it’s dark.” She’s fifty-something, in atiny walk-up in Belleville, and made us kebbewith pomegranate syrup,hummus and fattouch. “When night falls, I’m alone withsolitude.” Claire, ninety-three. * Nine months of illness,a year away from Beirut,of timor mortis at six on summer morningsawake in sweat-crumpled sheets. Now with departure,a duffel bag of troubleon your mind again, you sort out the books and clothes,throw the unused pills away. [End Page 37] *Used clothes and used books,past years packed in shopping bagsfor charity shops to diminish the clutter,to make room for the clutter of too many booksjust bought, and clothes from the soldesas if you had space, as if your years could expandinto numberless chapters. * Meaningless numbers,a birth year, death year, an age,the months of mourning. Her engravings on the wall,her book, and hers, near my bed. There is nothing inthe buzz of ginger or wineto pry tomorrow out of the sunlight’s hollowone-sided conversation. * Conversation ina room, the rain, on a pathgoing anywhere [End Page 38] and nowhere, and where would yourather be? Gnarled apple trees, hydrangea bushesmoon-green in late afternoon,an old man with keys to his allotment gardenand a bag of lettuces. * Dropped the laundry bagoff where they remember mefrom a year ago. Squeezing my pomegranatejuice, the portly grizzled man asked: Don’t we know you?Yes, I was here last spring andtwo years before that. Women, the same ones or not,are begging on Hamra Street. * Hamra Street perfume:sizzling man’ouche, red diesel,late-day narguilehs. In one café two beardedmen my age write in notebooks. I’m not at home, I’mnot homesick, not sure of myfooting and language. [End Page 39] I could learn Spanish in French.Learn ‘amiyeh in fus’ha? * If I order itin fus’ha, the waitress smiles,brings my glass of wine, understanding how much Ientirely don’t understand. So much forgottenof noun roots, branches of verbsI scratched in notebooks for weekly hours when nothingor everything could go wrong. * “Old’s” the wrong gender,like being the only girlon a team of boys, wrong race; the one black orbrown student in a white class, entirely aloneif there’s a problem and you’rein over your head or too reticent to askin your old lady wolf suit. * [End Page 40] Wolf of solitude,oud in late October wind,wolf words at wolf-hour. Is there a revolutionnot routed or turned riot? Too tired or too late,in always the wrong language,but I’d howl in it intuiting what he meant,not repeating what she...

Bad gene expression following effect of coenzyme Q10 on Wistar rat hippocampus with cerebral ischemia

Bad gene expression following effect of coenzyme Q10 on Wistar rat hippocampus with cerebral ischemia

Association of Pro-apoptotic Bad Gene Expression Changes with Benign Thyroid Nodules.

This study aimed to investigate the role of the mitochondrial apoptotic pathway in benign thyroid nodules. Paired samples of nodular and normal tissues were collected from 26 patients with nodular goiters undergoing thyroidectomy. Variable expression of Bcl-2, Bax and Bad genes were evaluated by quantitative PCR. Expression level of Bad gene in nodules was found to be significantly decreased compared to normal tissues (p=0.049). A positive correlation was observed between nodule size and Bad expression levels (correlation coefficient=0.563, p=0.004); and this correlation was stronger in hot nodules (n=18, correlation coefficient=0.689, p=0.003). No significant difference was observed between nodular and normal tissue expressions of Bax and Bcl-2. These results suggest that Bad expression correlates with the size of benign thyroid nodules and also its relatively lower expression in nodules, warrant further investigation.

A CRISPR Approach for a Common Inherited Disease: Researchers at Duke University Hope Gene Editing Can Eliminate Mutations That Lead to Duchenne Muscular Dystrophy.

Gene editing and CRISPR (a group of repeated DNA sequences in bacteria) typically target disease-causing mutated genes by eliminating the bad gene altogether, by correcting the problem DNA to restore proper gene functioning, or by modifying a different gene to compensate for the faulty gene's lost function. One research group at Duke University in Durham, North Carolina, however, is using a different strategy to fight one of the most common inherited genetic diseases: Duchenne muscular dystrophy (DMD).

Determinants of Monocyte Apoptosis in Cardiorenal Syndrome Type 1

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved. Material and Methods: We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression. Results: We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = – 0.76, p = 0.011, and ρ = – 0.72, p = 0.011). Conclusion: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1.

Genome editing protects hearing in mice

Researchers have used CRISPR-Cas9 genome editing to partially prevent hearing loss in mice with a genetic form of deafness. Traditional gene therapy, adding a functional gene to cells containing a missing or non-functional one, has been used before to treat genetic hearing loss in animals. But the new approach disrupts a bad gene instead of adding a good one. The study offers a possible treatment for a rare form of hearing loss in people caused by a single-base mutation in a gene called Tmc1. The mutation induces production of a protein that kills inner-ear hair cells, which sense sound waves. The mutation is dominant—a single mutation in one of the two gene copies causes people to lose hearing progressively. Traditional gene therapy cannot correct dominant mutations, so David R. Liu of Harvard University, Zheng-Yi Chen of Massachusetts Eye & Ear Infirmary and Harvard Medical School, and coworkers used CRISPR-Cas9 genome

BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy.

Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1-/- model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1-/- and Kcna1-/- Bad-/- double knockout mice to assess survival and seizure severity. We found that Kcna1-/- Bad-/- mice outlived Kcna1-/- mice by approximately 2 weeks. Kcna1-/- Bad-/- mice also spent significantly less time in seizure than Kcna1-/- mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy.

Apoptotic Effect of Nigella sativa on Human Lymphoma U937 Cells.

Objective:Nigella sativa is from botanical Ranunculaceae family and commonly known as black seed. Apoptotic effect of N. sativa and its apoptotic signaling pathways on U937 lymphoma cells are unknown.Materials and Methods:In this study, we investigated selective cytotoxic and apoptotic effects of N. sativa extract and its apoptotic mechanisms on U937 cells. In addition, we also studied selective cytotoxic activity of thymoquinone that is the most active essential oil of N. sativa.Results:Our results showed that N. sativa extract has selective cytotoxicity and apoptotic effects on U937 cells but not ECV304 control cells. However, thymoquinone had no significant cytotoxicity against on both cells. N. sativa extract increased significantly caspase-3, BAD, and p53 gene expressions in U937 cells.Conclusions:N. sativa may have anticancer drug potential and trigger p53-induced apoptosis in U937 lymphoma cells.SUMMARY This is the first study showing the apoptotic effect of Nigella sativa extract on U937 cells. Abbreviations used: CI: Cytotoxicity index, DMEM: Dulbecco's Modified Eagle Medium, HL: Hodgkin's lymphoma, MTT: 3-(4,5-dimethy lthiazol-2yl)-2,5-diphenyl tetrazolium bromide, RPMI: Roswell Park Memorial Institute medium.

The effect of MDMA and pentoxifylline drug on bad/bcl-xl gene dosage expression changes on rat liver

MDMA generally known as ecstasy, have deleterious effects on the serotonergic neurotransmitter system. Recent findings suggest that the liver and brain are major target organs of MDMA-related toxicities. Although most research is being dynamically performed on brain, however, the molecular mechanisms by which MDMA elicits adverse effects in both organs are poorly undrestood.The present study was performed to obtain evidence for molecular mechanism of apoptosis involved in MDMA-induced hepatotoxicity in rat liver after MDMAadministration. Moreover, the antagonistic effect of pentoxifylline was assessed on hepatotoxicity after MDMA administration. In this experimental study, sample size and power in each group were calculated as 10 rats with 95% confidence level and 5% confidence interval. In the study, four experimental groups were selected including Control Normal, MDMA, MDMA+PTX and PTX+MDMA. MDMA was dissolved in PBS and intraperitoneally injected three doses of 7.5mg/kg with two hours gap between doses. Pentoxyfilline also was injected as 100mg/kg, simultaneously with third dose of MDMA. After treatment, total RNA was isolated from liver tissue (5mg). Absorbance at 260nm, 280nm and 230nm were measured and immediately reverse transcription was performed. Included target genes were BAD and BCL -XL as pro-apoptotic and anti-apoptotic gene, respectively. After set up and validation, Real-Time PCR were performed and obtaining data were statistically analyzed to determine significantly differences between groups. Using Real-Time quantitative PCR results, BCL- XL gene expression ratio significantly increased in MDMA+PTX group. Moreover, BAD gene expression ratio increased and up-regulated in PTX+MDMA group ( P -value <0.001).Our study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results shown MDMA prompted apoptosis in liver and pentoxifylline protects hepatotoxicity after and befor taking MDMA.