bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALFABISABOLOL REVERSES THE MORPHOLOGICAL CHANGES INDUCED BY 5‐FU IN A MODEL OF INTESTINAL MUCOSITIS
Authors: Cerqueira Gilberto Santos , de Godoy José Roberto Pimenta , Lopes José , Sobrinho Osvaldo Pereira Costa , Medeiros Jand Venes Rolim , Martins Conceição Silva , da Silva Costa Deiziane Viana 
Published: November 2023

Introduction5‐Fluorouracil (5‐FU) is broadly used to treatment of breast and colorectal cancer. However, it induces side effects as intestinal mucositis. Studies several has been performed to reduce the 5‐FU‐induced intestinal injury. In this regard, the α‐bisabolol (1‐methyl‐4‐(1,5‐dimethyl‐1‐hydroxhex‐4 (5)‐enyl)‐cyclohexen‐1) (BISA) has not yet been investigated in treatment of the 5‐FU‐induced intestinal mucositis. BISA is a monocyclic sesquiterpene found in essential oils of a variety of plants such as chamomile (Matricaria chamomilla, Compositae, syn. M. recutita), arnica (Arnica amplexicaulis and A. chamissonis), sage (Salvia stenophylla) incanus Eremanthus, Vanillosmopsis arborea among others. The aim of this study was to investigate the effect of BISA in the 5‐FU‐induced intestinal mucositis.Methods and ResultsSwiss Mice (weighing 25 to 30 grams) received DMSO 2% (control) or 5‐FU (450 mg/kg, i.p., single dose). After 24h, BISA (50, 100 or 200 mg/kg, dissolved at DMSO 2%) was injected by orogastric gavage during three days and the animals were euthanized four hours after last dose of BISA. The mice's body weight were evaluated daily. The ileum segments were collected to evaluate following parameters: histopatological analysis, count number of mast cells, reduced glutathione (GSH) and myeloperoxidase (MPO) levels. The ileum segments were extracted, measured and processed by histology routine and dyed with Hematoxiline eosine, Masson' Trichrome with toluidine blue 1% for mast cell counting and with picrosirius red for the total collagen fibers. 5‐FU promoted accentuated weight loss, shortening villus, loss of crypt architecture, intense inflammatory cells infiltrate along ileum layer. Moreover, 5‐FU increased the number of mast cells (53,80±3.426); DMSO (22,20±2.21); BISA‐50 (53,80±3.426);BISA‐100 (31,60±1.621); BISA‐200(79,20±4.923) and MPO levels (6,532±1,354);DMSO (2,402±0,2190);BISA 50 (4,678±0,3424);BISA 100(3,382±0,3239); BISA 200 (4,330±0,6093) in ileum, as well as decreased GSH levels compared with control group. The experimental group presented increased vascular density compared to the control group.ConclusionThese results show that BISA had a protective effect against intestinal injury induced by 5‐FU. Moreover, we also showed that BISA reduces 5‐FU‐induced the mastocytosis. However, more tests are needed to evaluate the BISA mechanism in the 5‐FU‐induced intestinal mucositis.Support or Funding InformationFootnotes: This study received funding of CAPES.
Understanding Osteogenesis Through Penis Bone Evolution
Authors: Schultz Nick , Chipalkatti Naina , Dean Matthew D 
Published: November 2023

The exaggerated morphology, phylogenetic distribution, and potential reproductive function of the mammalian penis bone, baculum, have made it the subject of studies for centuries. Nevertheless, a detailed understanding of the evolution of the baculum is lacking. Our recent research indicates that the baculum has independently evolved 9 times and been lost at least 10 times, while the structure that it develops in, the phallus, has a single origin. This fascinating evolutionary trend implies that pre‐cursor cells within the penis of mammals can either modify conserved developmental pathways, or have evolved novel genetic networks to gain or lose the potential to develop a baculum. Here we distinguish these two hypotheses by studying osteogenesis in femurs and genitalia of three mammal species, mice, ferrets, and rabbits. These species represent two independent gains of the baculum (mouse, ferret), and a species without a baculum (rabbit), while the femurs of all three species have a single origin. Specifically, we will isolate pre‐cursor cells from the developing penis and femur to create a transcriptional atlas of osteogenesis across the three species. Since these bones commonly develop through endochondral ossification the transcription factor Sox9 will be used as a marker for osteogenesis. Sox9 positive cells will be identified through immunochemistry, isolated using FACS sorting, and then processed for RNA sequencing. Sequencing results will be compared both between species, and between bones to provide insight not only into the genetic regulation of baculum development, but will also enrich our understanding of osteogenic regulation.Support or Funding InformationThis work was supported by the National Institutes of Health grant #GM098536
Effect of Cyclophosphamide on the Rat Urinary Bladder and the Possible Protective Role of Thymoquinone
Authors: Sabry Hassan Sherif M. , Al‐Eyd Ghaith , Thomann Charity , Ahmad Zulfiqar 
Published: November 2023

BackgroundCyclophosphamide (CP) is a chemotherapeutic agent used for treating many neoplastic disease. Its application is limited now‐a‐days due to its multiple side effects including hemorrhagic cystitis. Thymoquinone (TQ) is one of the active ingredients of Nigella sativa seeds, known for its healing potentials.Aim of studyThe current study has been carried out to examine the protective effect of 2 different doses of TQ against CP‐induced oxidative injury in the urinary bladder in rat. In addition to the possible mechanism through which TQ produces its protective effect.Methods5 groups of 40 rats were used in this study. An untreated control group receiving no treatment, a sham control group where TQ (10 mg/kg/day) was administered using gastric gavage, in a single oral dose for 10 consecutive days. A toxicity group where CP‐induced toxicity was induced via 100 mg/kg, intraperitoneal for 2 days. In addition to 2 protection groups, both receiving CP at a dose of 100 mg/kg, intraperitoneal for 2 days but receiving 2 different doses of TQ, at concentrations of 10 mg/kg/day for 10 days and 100 mg/kg/day for 5 days.ResultsCP caused alteration of the urinary bladder histology in rat, with significant oxidative stress (ROS), as revealed by the reduction in the catalase (CA) and glutathione reductase (GR) in blood, in addition to increased lipid peroxidation to compensate for the ROS as revealed by the increase in the malondialdehyde levels (MDA) in blood. CP also induced cell death, as revealed by the activation of caspase‐3 in blood. Post treatment with TQ (at a dose of 100mg/kg/day for 5 consecutive days), however reduced CP‐induced ROS and apoptosis.ConclusionConcomitant use of TQ with CP could ameliorate the CP‐induced toxicity on the rat urinary bladder via its antioxidant and antiapoptotic effects.Support or Funding InformationSelf Fund
Development of a Porcine Model to Study the Aortic Plexus and Innervation to the Internal Urethral Sphincter: Implications for Preventing Retrograde Ejaculation
Authors: Beveridge Tyler S. , Groh Adam M. , Moore Colin W. , El‐Warrak Alexander , Johnson Marjorie , Power Nicholas , Allman Brian L. 
Published: November 2023

INTRODUCTIONThe sympathetic nerves and ganglia overlying the abdominal aorta in humans are symmetrically organized into a bilateral network called the aortic plexus that must be spared during retroperitoneal surgery in order to maintain antegrade ejaculation. It is well established that complete resection of the aortic plexus causes retrograde ejaculation (RE) that results from de‐innervation of the internal urethral sphincter (IUS). At present, however, it remains uncertain which specific nerves of the aortic plexus control the IUS, and thus, which nerves are important for ejaculation.To ultimately determine which nerves are imperative to maintain ejaculation, the present study aimed to first establish the pig as a comparable model of the human aortic plexus in both structure and function. It was our working hypothesis that the pig exhibits comparable anatomy in terms of gross organization, number of infrarenal splanchnic nerves and constituent ganglia, and that stimulation of the left and right hypogastric nerves (homologous to the human superior hypogastric plexus) would evoke contraction of the IUS.METHODSThe porcine aortic plexus was examined in 18 boars by gross dissection followed by a histological examination to differentiate ganglia from nerve. Innervation of the IUS was examined using a lesion‐and‐test method, in which stimulation with a bipolar electrode was used to excite the hypogastric nerves distal to the caudal mesenteric ganglia before and after transection (n=5).RESULTSAs predicted, the anatomy of the porcine aortic plexus appeared comparable to humans, exhibiting two bilateral cords that were supplied by two or more infrarenal lumbar splanchnic nerves. Right and left caudal mesenteric and spermatic ganglia were invariably observed adjacent to their respective arteries, and given their topography within the plexus, they appear homologous to the prehypogastric, inferior mesenteric and spermatic ganglia in humans, respectively. At the junction of the upper infrarenal lumbar splanchnic nerves, two additional ganglia were observed within the cords of the porcine aortic plexus (prevalenceright = 4/8; prevalenceleft = 3/8); these structures have not been reported in humans. Electrostimulation of each hypogastric nerve evoked bladder neck contraction (ΔPright = 6.2 ± 2.2 mmHg, ΔPleft = 4.5 ± 2.2 mmHg), which was abolished following transection.CONCLUSIONSCollectively, our results confirm that the pig represents an effective preclinical model for studying not only the structure and normal function of the aortic plexus, but also the implications of unintended surgical trauma on the delicate nerves controlling ejaculation.Support or Funding InformationThis work is supported by CIHR
Cell‐matrix interactions in temporomandibular joint homeostasis
Authors: Reed David A 
Published: November 2023

Mechanobiological signaling is a critical regulator of tissue homeostasis in the temporomandibular joint (TMJ), and is achieved through chondrocyte receptor mediated interactions with the pericellular microenvironment. Mechanical and/or inflammatory stress is hypothesized to disrupt these interactions and promote cartilage degeneration. However, defining select and specific cell‐matrix derived signals in the context of TMJ degenerative pathophysiology has yet to be achieved. Here we evaluate the interaction of type VI collagen, an abundant pericellular matrix molecule that affects the material properties of the chondrocyte microenvironment, with nerve/glial antigen 2 (NG2), a transmembrane proteoglycan that binds with type VI collagen. In other cell types, proteolysis of the NG2 ectodomain internalizes an intracellular domain, influencing transcriptional activity in the cell through a PDZ binding motif. Here we test the hypothesis that mechanical and/or inflammatory stress in the TMJ will be associated a spatiotemporal dysregulation of NG2‐type VI collagen interactions and high levels of internalized NG2. In vivo, degeneration was induced in the TMJ of male c57 mice using unilateral partial discectomy. In vitro, mandibular condylar cartilage explants were exposed to a 10 N, 1 Hz compressive load for five days in a compression bioreactor environment. NG2‐type VI collagen colocalization was calculated from immunofluorescence confocal microscopy, and confirmed with proximity ligation assay. In vivo, non‐surgical controls yielded NG2‐type VI collagen colocalization in articular, prechondroblastic and chondroblastic cells (n = 3). High levels of internalized NG2 were observed in hypertrophic cells. Following degeneration, colocalization values decreased (n = 3; p < 0.05) and internalized NG2 levels increased in articular cells (n=3). In vitro, exposure to mechanical stress yielded similar results, with high levels of internalized NG2 in articular and hypertrophic chondrocytes. These data illustrate that NG2 colocalizes with pericellular type VI collagen in mandibular chondrocytes, and that mechanical and/or inflammatory stress affects colocalization and NG2 internalization. Future work will define the functionality of internalized NG2 in the pathophysiology of degenerative temporomandibular disorders.Support or Funding InformationThe Department of Oral Biology, UIC College of Dentistry
Age‐Based Degenerative Joint Disease of Intracapsular Anatomy of the Knee: A Cadaveric Study
Authors: Immonen Jessica , Siefring Chris , Sanders Luke 
Published: November 2023

The objective of this study is to determine specific degenerative changes to intracapsular anatomy of the knee joint with aging. The Center for Disease Control states that approximately 14% of Americans 25–65 years old and 33.6% of Americans 65+ experience symptoms of osteoarthritis (OA) and/or degenerative joint disease. The knee joint heavily contributes to OA‐related deaths and hospitalizations in the United States and these values are likely underestimated. Metamorphic analyses to cadaveric intracapsular anatomy of the knee were performed using Image Pro software on three age populations: < 70 years old, 70–79 years old and greater than or equal to 80 years old. The articular cartilage of the medial tibial plateau in the greater than or equal to 80 years old specimens showed a 1.7‐fold increase in surface area degeneration (mm2) compared to 70–79 years old specimens (P<0.05). The articular cartilage of the lateral tibial plateau experienced a 15% and 26% approximate loss in surface area when comparing the < 70 years old age group to the 70–79 years old age group and the greater than or equal to 80 years old age group, respectively. The medial meniscus experienced degenerative changes with aging. These values were expressed as decreases in tibial plateau surface area coverage. Specimens < 70 years old had an average of 49% coverage of the medial tibial plateau whereas the 70–79 years old and the greater than or equal to 80 years old age groups had approximately 38% and 36% coverage, respectively. No major degeneration with aging was seen on the lateral meniscus. 100% of the specimens contained either the anterior meniscofemoral ligament or the posterior meniscofemoral ligament. This additional support to the lateral meniscus could reduce its degeneration as well as the degeneration of underlying lateral articular cartilage. The anterior cruciate ligament (ACL) experienced substantial degenerative thinning with aging. The 70–79 years old specimens had a 1.2‐fold decrease in average ACL circumference (mm) compared to the < 70 years old specimens (P<0.001). The greater than or equal to 80 years old specimens had a 1.24‐fold decrease in ACL circumference compared to the < 70 years old specimens (P<0.001). Weakness of the tensor fascia lata muscle, excessive foot pronation during gait, obesity and skeletal pathology such as shortening or fracture of the femur all may contribute to the increased lateral degeneration with aging on the tibial plateau compared to the medial respects. Contrarily, the medial respects of the joint may experience accelerated degeneration of the meniscus and articular cartilage due to normal compressive forces during gait and obesity. ACL thinning during aging may be leading to substantial articular cartilage degeneration given the cruciate ligaments and the musculature of the knee joint are the primary restraints that combat shearing forces at the knee joint.Support or Funding InformationInternal Grant from RMUoHP for Protocol No. 150430‐04
Effects of High‐Fat Diet and Age on the Blood Lipidome and Circulating Endocannabinoids of Female C57BL/6 Mice
Authors: Pati Sumitra , Krishna Saritha , Lee Jung Hwa , de La Serre Claire , Harn Donald , Wagner John , Filipov Nikolay , Cummings Brian 
Published: November 2023

Obesity is a growing public health concern that increases the risk of inflammatory and metabolic disorders. While the mechanisms linking obesity and metabolic disorders remain unknown, several studies suggest that alterations in lipid‐mediated metabolism play a significant role. The growing literature demonstrating the complexity of the plasma lipidome and its dysregulation within the context of several diseases has led to studies aimed at identifying lipid markers of obesity and/or type 2 diabetes. We assessed the effects of dietary fat and aging at the level of the lipidome using shotgun lipidomics with electrospray ionization‐mass spectrometry (ESI‐MS) and did so in females. Blood lipid profiles of female C57BL/6 mice following high‐fat diet (HFD) and low‐fat diet (LFD) consumption for short (6 weeks), long (22 weeks), and prolonged (36 weeks) periods were analyzed to evaluate the effects of HFD feeding. To compare lipid alterations with metabolic and liver regulation, we also examined glucose tolerance, insulin sensitivity, endocannabinoid levels, plasma esterase activity, and liver homeostasis. Multivariate analysis of blood lipidomic data indicated differences in the lipid profiles between HFD‐ and LFD‐fed mice with the most notable differences following 6 weeks of consumption. Age‐related alterations demonstrated the most striking effect on the lipidome where the most variation was observed between 6 week and 22–36 week treatment groups, irrespective of dietary treatment. Both HFD‐consumption and age altered the relative abundances of lipid species belonging to phospholipid, fatty acyl, and glycerolipid classes. Interestingly, HFD feeding also affected endocannabinoid levels in an age‐dependent manner. Plasma esterase activity was increased by HFD feeding at all time points, with the most pronounced effect following 6 weeks of consumption. Liver mRNA levels of three important metabolic regulators, PPARα, PPARγ, and CD36, were all affected by HFD consumption. These findings indicate an interaction between dietary fat consumption and aging with widespread effects on the blood lipidome, which may provide a basis for identification of female‐specific obesity‐ and age‐related lipid biomarkers.Support or Funding InformationThis project was supported in part with funds from the University of Georgia's Obesity Initiative (http://obesity.ovpr.uga.edu/).
High‐fat diet increases Clostridium clusters XIVa in obese rodents
Authors: Jiao Na , Baker Susan S , Nugent Colleen A. , Tsompana Maria , Guan Lingyu , Wang Yong , Buck Michael J , Genco Robert J , Baker Robert D , Zhu Ruixin , Zhu Lixin 
Published: November 2023

BackgroundA number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we aim to obtain an unbiased evaluation of structural and functional changes of the gut microbiota of diet‐induced obese rodents using a meta‐analysis.MethodsOur analysis included nine 16S sequencing datasets generated with high‐fat‐diet (HFD)‐induced obese mouse or rat models. The raw sequencing data of all nine studies were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways using PICRUSt.ResultsNo significant difference was observed for alpha diversity and Bacteroidetes : Firmicutes (B/F) ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, Erysipelotrichi were dominant classes in obese rodents but gut microbiota compositions varied among studies. Meta‐analysis of the nine datasets identified 12 differential taxa and 67 differential pathways between obese and lean animals. In obese rodents, we observed increased abundance of Dorea, Oscillospira, and an unassigned genus of Clostridiales. These three genera belong to Clostridium clusters XIVa, known for polysaccharide fermentation. Enterococcus and Lactococcus also increased in obese animals which could release bile salt hydrolase (BSH) that convert conjugated bile acids into free bile acids through deconjugation. Compared to lean animals, differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, pentose phosphate pathway, fatty acid biosynthesis, glycerolipid metabolism and membrane transporter pathways. These pathways converge in the function of carbohydrate metabolism, biosynthesis of lipid and energy transportation.ConclusionHFD‐induced obesity alters the structure and function of murine gut microbiota. Altered production of short‐chain fatty acid, lipopolysaccharides, and bile acids by gut microbiota could impact lipid and glucose metabolism, insulin resistance and systemic inflammatory status of the obese rodents.
Pectin and Its Hydrolysates Stimulate Intestinal Mucin Secretion
Authors: Hino Shingo , Morita Tatsuya 
Published: November 2023

ObjectivesSoluble dietary fibers (SDF) increase small intestinal mucin secretion by increasing the number of goblet cells in proportion to the viscosity of the SDF ingested. Our recent study showed in rats that low methoxyl pectin (LPC) enhanced mucin secretion irrespective of goblet cell number in the small intestine. Mucin secretory effects of LPC were also confirmed in vitro using HT‐29MTX cells, suggesting that pectin directly stimulates mucin secretion from the individual goblet cells. The present study aimed to characterize the mucin secretory effect of pectin among SDF and to clarify active components of pectin related to mucin secretion.Materials & MethodsHT‐29MTX cells were cultured with 6.25–100 mg /L of the respective SDF including pectin for 24 h. The culture media were gathered and subjected to MUC5AC determination. RNA was extracted from the cells and subjected to gene expression analysis for MUC5AC. Pectin hydrolysates were obtained from citrus pectin using pectinase (polygalacturonase) and fractionated by diethylaminoethanol cellulose column. Mucin secretory effects of the hydrolysates were also examined.Results & FindingsOnly pectin stimulated mucin secretion from HT‐29MTX cells. Mucin secretory effects of pectin were observed irrespective of molecular size, their origins and degree of methoxylation. Pectin hydrolysates also stimulated mucin secretion accompanied by the increase in MUC5AC expression, but oligo‐galacturonic acids did not. The minimal effective concentrations of pectin hydrolysates were 100‐fold lower than those of pectin. Sugar composition analysis showed that pectin hydrolysates contained higher concentrations of rhamnose and neutral sugars compared with the pectin. From these results, it is plausible to assume that hairy region (rhamnogalacturonan carrying side chains) rather than smooth region (homogalacturonan) in the pectin molecule is responsible for mucin secretory effects.ConclusionAmong the various SDF tested, only pectin and pectin hydrolysates have exerted significant increases in mucin release from the cells. Clearly, they act as mucin secretagogue.