bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis‐Inducing Herbs for Prostate Cancer Prevention and Treatment
Authors: Meng Jing , Hawthorne Benjamin , Lund Kaleb 
Published: November 2023

BackgroundProstate cancer is the most common non‐skin cancer in men. The conventional treatment regimen for prostate cancer is chemical castration, which has adverse effects, and tumors often recur following treatment. Therefore, developing an alternative therapeutic plan for prostate cancer is very much desirable. The purpose of this study is to identify and validate natural herbs that can induce apoptosis of prostate cancer cells.MethodsSaw Palmetto (Serenoa repens, I), Sanqi (Panax notoginsengI), and Ban Lan Gen (Isatis tinctoria) are extracted in alcohol at various concentrations. We performed HPLC to characterize these herbs, and then treated LNCaP prostate cancer cells with the ethanol extracts of these herbs. The viability of the treated and control cells was assessed by MTT Cell Proliferation Assay and flow cytometry. Real‐Time Quantitative PCR was performed to determine the expression levels of apoptotic genes.ResultsWe show here that Saw Palmetto (Serenoa repens, I), Sanqi (Panax notoginsengI), and Ban Lan Gen (Isatis tinctoria) have the corresponding standard HPLC molecular profiles. They decreased the cell viability and enhanced apoptosis of LNCaP cells based upon MTT assay and flow cytometric analysis. Our preliminary quantitative RT‐PCR data also showed the elevated the expression levels of apoptotic genes in LNCaP cells treated by the herb extracts.DiscussionThe data show that cell proliferation of prostate cancer cells is reduced by treatment in vitro of the herbs studied. Despite the limitations of this in vitro study, these data provide exciting evidence for the anti‐cancer properties of these herbs and could contribute to new treatments for prostate cancer.Support or Funding InformationThis work was funded by Grant 4 and 13 from Bastyr University.
The Role of Aminoguanidine on the Epididymis of Diabetic Rats: A Histological Study
Authors: Othman Manal Ahmed 
Published: November 2023

BackgroundDiabetes mellitus (DM) is a degenerative disease with alteration in carbohydrate homeostasis that harmfully affect the male reproductive function. One of the diabetic complications is the production of advanced glycation end products (AGEs) that generate reactive oxygen intermediates. Consequently this might be deleterious to reproductive organs and lead to the development of spermatogenic dysfunctions. Aminoguanidine, is an AGEs inhibitor and therefore it might ameliorate the diabetic complications. The epidydimis in an important structure in the male reproductive system, where maturation and storage of spermatozoa take place. The aim of this work was to demonstrate the effect of aminoguanidine treatment on the epididymis of adult diabetic male rats.Materials and MethodsA total number of 18 male Sprague Dawley (SD) rats (average weight 200 gm) were divided into three groups of 6 animals each. Group I: was the control group. Group II: included the diabetic rats which were injected a single dose of 80 mg/kg (IP) streptozotocin (STZ) in sodium citrate. Group III: included rats with STZ‐induced DM (as in group II) that were orally administered aminoguanidine through a gastric tube at a dose of 4 mg/kg/day for 3 months from the third day after the induction of DM until the time of sacrifice. After sacrificing the animals, the epididymis was obtained from the three assigned groups and processed for light microscopic evaluation.ResultsIn the diabetic animals, the epidydimal tubules showed variable degenerative changes in the form of decrease sperms in the tubules, with condensed nuclei in some epithelial cells. A notable finding was the presence of variable amount of white blood cells inside the lumen of the tubules which might indicate an inflammatory process. There were irregular increase in PAS staining as well as disrupted collagen content. On the other hand, diabetic rats treated with aminoguanidine showed improvement in their epididymal structure.ConclusionDiabetes mellitus resulted in degenerative changes in the epididymis of SD rats. These changes were enhanced by the administration of aminoguanidine which may be useful in the treatment of diabetic reproductive complications.
Dysregulated Inflammation in Response to Hypoxia‐Confounded Injury
Authors: Mayeux Jacques , Adesina Sherry , Caesar Christa , Naylor Petrina Barnett , Woodard‐Grice Alencia 
Published: November 2023

Traumatic limb injury can cause extensive blood vessel damage that impairs oxygen and nutrient delivery to nearby tissues, resulting in a hypoxic state. The normal course of tissue repair involves a proper balance of pro‐ and anti‐inflammatory signaling; this balance is essential for tissue recovery as it aids in the destruction, containment or removal of pathogens and facilitates the repair of damaged tissue. However, in periods of extended hypoxia‐confounded injury, inflammation may become dysregulated. The mechanisms by which extended hypoxia may influence inflammatory cell activation during the acute recovery period are unknown. We therefore sought to create an in vitro wound model of sustained hypoxia to investigate inflammatory cell activation during this acute recovery period. We hypothesized that sustained hypoxia would result in greater immune cell activation over 72 hours compared to normoxia.We completed several experiments utilizing human monocytes (U937 cells), human dermal fibroblasts (HDFs), and human umbilical vascular endothelial cells (HUVECs) exposed to normoxia (~21% O2) or hypoxia (~1% O2) for 24, 48, or 72 hours. We sought to assess the impact of sustained hypoxia on cell proliferation (scratch wound assay) and immune cell activation (macrophage adhesion; transmigration of macrophages; expression of cell surface markers CD11b and CD14) at each of the time points listed above.We found that hypoxia impaired endothelial cell proliferation in a scratch wound assay, decreasing their ability to cover the gap area after 72 hours. We additionally found that macrophage transmigration was increased in response to hypoxia and that this result was correlated with increased immune cell proliferation as evidenced by increased cell surface expression of CD11b and CD14. We believe these results will provide valuable insight into the effect of sustained hypoxia on inflammatory signaling, and perhaps more importantly, the time course of signaling changes following hypoxia‐confounded injury.
12‐HETE Signaling Through the G Protein‐Coupled Receptor 31 (GPR31) Regulates Pancreas Development and Disease
Authors: Anderson Ryan Mallory , Hernandez‐Perez Marimar , Tersey Sarah , Samala Niharika , Maier Bernhard , Mirmira Raghavendra G. 
Published: November 2023

Inflammation is essential for pathogen defense and tissue repair, but drives many pathologies when dysregulated. For instance, inflammation plays a critical role in pancreatic β cell dysfunction, and is a hallmark of both type 1 and type 2 diabetes. Thus, the molecular pathways initiating and escalating islet inflammation are prime targets for novel diabetes therapeutics. One such inflammatory mediator, 12‐hydroxyeicosatetraenoic acid (12‐HETE), is an oxygenated derivative of arachidonic acid generated by 12‐Lipoxygenase (12‐LO). Pancreatic deletion of 12‐LO protects obese high fat diet‐fed mice from glucose intolerance, and improves insulin secretion in cytokine‐treated islets in a 12‐HETE‐dependent manner. In vitro assays have shown that 12‐HETE can ligate the G protein coupled receptor GPR31, but little is known about the activation of this pathway or its role in islet biology; we hypothesized that the pancreatic actions of 12‐HETE are mediated in part by GPR31. Accordingly, when the beta cell line βTC3 was treated with 12‐HETE, we measured an induction of ER stress markers and suppression of oxidative stress pathway markers; these effects were blocked by shRNA knockdown of Gpr31, suggesting that 12‐HETE/GPR31 signaling is a node of convergence for stress pathways during inflammatory response in mouse β cells. To further clarify the in vivo roles of this pathway, we generated loss‐of function zebrafish models for both 12‐lipoxygenase (alox12) and gpr31 using morpholinos and CRISPR/Cas9. Loss of alox12 diminished 12‐HETE production and unexpectedly impaired pancreatic growth. Similarly, the loss of gpr31 resulted in a severe reduction of pancreas tissues via impaired differentiation. We propose that 12‐HETE signaling via GPR31 is an important paracrine and/or autocrine pathway involved in diabetes pathogenesis that is also essential for pancreas formation during development.Support or Funding InformationThis work is supported by NIDDK grant R01 DK105588 02 to RM
Endomucin is necessary for pathologic retinal neovascularization in vivo
Authors: D'Amore Patricia A. , Park‐Windhol Cindy A. , Saint‐Geniez Magali 
Published: November 2023

Many ocular pathologies, including wet age‐related macular degeneration (AMD) and the retinopathy of prematurity, are characterized by abnormal neovascularization. Endomucin‐1 (EMCN), is an endothelial cell‐specific, sialic‐rich glycoprotein. We have shown that EMCN is necessary for VEGF‐mediated proliferation, migration and tube formation by human retinal endothelial cells in vitro and for normal retinal vessel development in vivo. Motivated by these finding, we examined the role of EMCN in the formation of pathological vessels using murine oxygen‐induced retinopathy (OIR) and the laser‐induced choroidal neovascularization (CNV) models. Intravitreal delivery of siEMCN to P12 mice following exposure to hyperoxia led to a significant reduction in avascular area (14.2±2.6% vs 22.6±4.7%, P<0.05) and neovascularization (2.6± 0.3% vs 3.5% ± 0.5%, P<0.05) in mice with EMCN knockdown at P17 compared to siCtrl mice. In the laser‐induced model of CNV, comparison of fluorescein angiograms at day 14 indicated that the CNV lesions in siEMCN‐treated mice were smaller and significantly less leaky than in mice (32.2±1.4% vs. 40.6±4.1%, P<0.05). Our data indicate EMCN reduction/neutralization may be a potential therapy for treating pathologic ocular neovascularization.Support or Funding InformationThis work was supported by EY5318 and EY26539 (PD'A), a Knight's Templar fellowship (CPW) and P30EY003790.
Can Molecular Hippocampal Alterations Explain Behavioral Differences in Prenatally Stressed Rats?
Authors: Woolard Emily Alice , Miller Colette , McDaniel Katherine , Beasley Tracey , Oshiro Wendy , Moser Virginia 
Published: November 2023

Studies in both humans and animals have shown that prenatal stress (PNS) can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=12–13/treatment) were subjected to several non‐chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non‐stressed dams on GD 12, but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD 22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition task. Stressed offspring showed increased reversal path length on the Morris water maze. This result indicates changes in the behavioral performance of offspring. On PND 91–92, offspring were euthanized and hippocampal tissue was collected. Genotypic outcomes of PNS were assessed by quantifying hippocampal mRNA expression of five select genes thought to be implicated in these behaviors. The select genes were Brain‐Derived Neurotrophic Factor (Bdnf), Tropomyosin Receptor Kinase 2 (Trk2), DNA Methyltransferase (Dnmt) 1, Dnmt3a, and Dnmt3b, with Hypoxanthine Guanine Phosphoribosyltransferase (Hprt) used as an endogenous control. PNS female offspring had significantly lower Dnmt3b expression than controls (p=0.02). A trend showed PNS female offspring had reduced Dnmt3a levels compared to controls, suggesting additional alterations in basal levels of hippocampal mRNA expression (p=0.06). These preliminary findings support a role for hippocampal gene expression in long‐term changes in offspring of prenatally stressed dams.This is an abstract of a proposed presentation and does not reflect US EPA policy.
The Changes of the Learning and Memory Ability after Stimulation by STN‐DBS in Parkinson's Disease Rats
Authors: Hao Chunyan , Duan Hubin , Li Hao , Wang suping , Zhang Ce , Pan Lijuan 
Published: November 2023

ObjectiveTo investigate the changes of the learning and memory ability after stimulated by subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's Disease (PD) rats.Methods55 healthy male SD rats were randomly divided into normal control group (n=10), PD group (n=15), sham stimulation group (n=15) and stimulation group (n=15). Stimulation and sham stimulation groups were planted in unilateral STN‐DBS. STN‐DBS in stimulation group was powered on and was stimulated 7 consecutive days at the regular time, while Sham stimulation group complied with the same program except power on the STN‐DBS. The apomorphine rotation was observed at pre‐stimulation and post‐stimulation. The latency to find the platform, swimming speed, swimming distance and crossing times were detected with Morris water maze.ResultsThe symptoms of PD rats were improved significantly after stimulated by STN‐DBS. Compared with PD model group and sham stimulation model group, not only escape latency of rats in the DBS stimulated model group was decreased (P < 0.01), but also swimming speed (P < 0.05)and swimming distance (P < 0.05) were descend. The crossing times、 swimming distance and swimming time in which the platform located of PD model group(p < 0.05) and sham stimulation model group(p < 0.05) were definitely lesser than stimulation model group.ConclusionSTN‐DBS stimulation not only can improve the ability of cognition, but also delay the condition worsen..Support or Funding InformationThis study was supported by the National Natural Science Foundation Youth (Fund No.30600637), China Postdoctral Foundation (Fund No.2014M561207), Shanxi Scholarship Council of China(Fund No. 2011‐096 and Key projects No.4), The science and technology research projects of health department of Shanxi province (FundNo. 201301068), Shanxi Province Basic Research Program Youth Science and Technology Research Fund (Fund No.201601D011119).,
Anti‐tumor Activity of PCAIs in 3D Cell Culture and Mice Models
Authors: Salako Olufisayo O. , Nkembo Augustine T. , Ntantie Elizabeth , Lamango Nazarius S. 
Published: November 2023

PURPOSEOf the four molecular subtypes of breast cancer, TNBC is the most difficult to treat due to its lack of biomarkers and targeted therapies. Metastasis, which is characterized by cancer cell migration and invasion of distal organs, is highly prevalent in TNBC, making the disease harder to manage while lowering survival rates. The PCAIs, developed and modeled around the post‐translational modifications of regulatory proteins such as K‐Ras, were designed to inhibit the interactions of overactive monomeric G‐proteins. These proteins operate downstream of EGFR which is overexpressed in 60% of TNBC cases and are vastly involved in regulating cell survival, motility, apoptosis, and ultimately cancer progression. Previous work in our lab has shown that treatment of various cancer cell lines with PCAIs leads to cell cycle arrest, suppression of cell viability, inhibition of monolayer cell migration and invasion, and induction of caspase 3/7‐mediated apoptotic death. The purpose of this study was to determine the effectiveness of PCAIs at impeding the trademarks of cancer progression in 3D cell culture and in in vivo models.METHODSMDA‐MB‐231 cells were used in 3D cell culture assays to assess the PCAIs' ability to inhibit spheroid formation and invasion while inducing apoptosis. TNBC mice xenografts were used to determine the efficacy of PCAIs in vivo.RESULTSCompounds NSL‐BA‐055 and NSL‐BA‐040 were the most potent of the PCAIs, halting the formation of compact spheroids at 1.0 and 2.0 μM while significantly inhibiting spheroid invasion at 0.2 and 1.0 μM, respectively. Both compounds induced apoptosis and completely obliterated compact TNBC spheroids at 5.0 μM. Five and 10 mg/kg NSL‐BA‐040 inhibited the growth of TNBC xenograft tumors by 60.1 and 71.2%, respectively.CONCLUSIONThe PCAIs' ability to prevent spheroid formation and invasion while inducing spheroid apoptosis suggests their ability to prevent metastasis, tumor formation, growth and potential as effective therapies for TNBC.Support or Funding InformationThe research reported in this publication was supported by the National Cancer Institute (NCI) and National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under Grant SC1CA190505 and by the National Institute On Minority Health and Health Disparities (NIMHD) of the NIH under Award Number G12 MD007582 (previous award NIH/NCRR/RCMI G12 RR03020). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Arginase Inhibition Suppresses Breast Cancer Cell Proliferation
Authors: Shatanawi Alia , Qasrawi Heba 
Published: November 2023

Breast cancer is the second most common cause of cancer worldwide. It is recognized to be the most common cancer in women. It is also considered as the second leading cause of cancer death in women in the United States. There is accumulating evidence of increased arginase activity in patients with breast cancer. Arginase, an enzyme of the urea cycle, catalyzes the hydrolysis of L‐arginine to urea and L‐ornithine. L‐ornithine is converted to polyamines by the enzyme ornithine decarboxylase (ODC). Polyamines such as spermidine and spermine have an important role in cell proliferation. Hence, polyamines are also found to have an important role in tumor development and growth. Levels of polyamines are found to be 2–3 times higher in breast cancer cells than in normal surrounding tissue.We studied the effects of arginase inhibition on breast cancer cells and endothelial cells in vitro. Our experiments utilized MCF‐7 breast cancer cells or bovine aortic endothelial cells. Arginase activity was measured in cells treated with or without the novel arginase inhibitor; 2(S)‐amino‐6‐boronohexanoic acid (ABH). Additionally, the effect of ABH treatment on cells proliferation in vitro was determined using cell proliferation assay.Our results show that arginase inhibition caused a concentration dependent suppression of MCF‐7 cell proliferation with a maximum inhibitory concentration of 500 μM. This dose of ABH resulted in a 30% decrease in cell proliferation versus untreated controls. Arginase activity was measured in cells treated with ABH and was decreased by 60% versus controls. Interestingly, while ABH inhibited arginase activity in endothelial cells, it did not have any effect on the proliferation rate of endothelial cells. Our results indicate that arginase can be considered a new therapeutic target for suppressing breast cancer cell growth. Arginase inhibitors represent a potential cancer therapy in tumors with elevated arginase activity.Support or Funding InformationThe University of Jordan Deanship of Research
Involvement of Polo‐like kinase 1 (Plk1) in tumor growth and epithelial‐mesenchymal transition of tamoxifen‐resistant breast cancer
Authors: Jeong Sung Baek , Kang Keon Wook 
Published: November 2023

The most common therapy for estrogen receptor‐positive breast cancer is anti‐hormone therapy such as tamoxifen treatment. However, one‐third of the patients acquires tamoxifen resistance and become a serious clinical problem. Polo‐like kinase 1 (Plk1) is a key regulator for the completion of G2/M phase cell cycle. When we assessed Plk1 expression in six chemo‐resistant cancer cell sets, we found that Plk1 and its downstream phosphatase, Cdc25c were selectively overexpressed in tamoxifen‐resistant MCF‐7 (TAMR‐MCF‐7) breast cancer cells. Real‐time monitoring of cell proliferation also showed that BI2536 (ATP‐competitive Plk1 inhibitor)‐mediated inhibition of cell proliferation was more sensitive in TAMR‐MCF‐7 cells than the parent MCF‐7 cells. Moreover, we observed that BI2536 suppressed the expression of epithelial‐mesenchymal transition (EMT) marker proteins and 3D‐spheroid formation in TAMR‐MCF‐7 cells. By using TAMR‐MCF‐7 cells‐implanted xenograft and spleen‐liver metastasis models, we observed that BI2536 inhibited tumor growth and metastasis in vivo. Our results propose that Plk1 could be a novel target for the treatment of tamoxifen‐resistant breast cancer.Support or Funding InformationThis work was supported by a grant (2014M3A9A9073788) from National Research Foundation of Korea, Republic of Korea.
A Novel Hydrogen Sulfide Donor, JK1 Protects the Heart Against Cardiac Hypertrophy and Heart Failure
Authors: Li Zhen , Organ Chelsea L. , Kang Jianming , Xian Ming , Lefer David J. 
Published: November 2023

Background and HypothesisHydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One major limitation in the development of H2S‐based therapy is a lack of evidence supporting its cardioprotective effects in a clinically relevant scenario that mimics heart failure in humans. A second limitation related to the development of H2S therapeutics for heart failure is the very poor pharmacokinetic profile of most H2S‐donating agents. In the present study we tested the efficacy of a novel H2S donor, JK1, with controlled H2S release and increased half‐life compared to traditional H2S‐releasing agents. We evaluated JK1 in a clinically relevant murine model of transverse aortic constriction (TAC) induced heart failure (HF). We hypothesized that delayed administration of JK1 would protect the myocardium against TAC‐induced heart failure.MethodsMale C57/BL6J at 10 weeks (wks) of age were subjected to TAC (27G needle) for 12 wks. Optimal dosing of JK1 was determined from preliminary studies of in vivo myocardial ischemia and reperfusion in which 100 μg/kg JK1 treatment reduced myocardial infarct size from 48.19% to 17.44%. JK1 (100 μg/kg/d, n=16) or control compound (100 μg/kg/d, n=15) were administered (i.p.) starting at 3 wks post TAC. Echocardiography was performed at baseline and following TAC to assess cardiac function.ResultsDelayed treatment of JK1 significantly preserved left ventricular (LV) ejection fraction (LVEF 49.7% vs. 36.2%, p < 0.001), reduced left ventricular dilation (LVEDD/LVESD in mm): 3.77/2.81 vs. 4.34/3.50, p < 0.001), and attenuated eccentric hypertrophy (IVSD in mm: 0.84 vs. 1.00, p < 0.01. LVPWd in mm: 0.78 vs. 0.89, p < 0.05) at 12 wks post TAC as compared to Control. Complete data for LVEF and % LV fractional shortening (FS) are shown below.ConclusionThese results demonstrate that delayed administration of JK1 significantly preserves LV function and attenuates adverse remodeling in HF. Studies are currently underway to define the molecular mechanisms involved in JK1 mediated cardioprotection.Support or Funding InformationAcknowledgement: This work was supported by the National Institutes of Health (R01HL116571).