bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of post‐injury anti‐miR‐181a and anti‐miR‐200c intravenous treatment in protection against experimental stroke in aged mice
Authors: Griffiths Brian , Xu Lijun , Stary Creed 
Published: May 2022

IntroductionStroke remains the second leading cause of death worldwide and the primary cause of long‐term disability in the US. To date, the only pharmacological treatment for stroke remains tissue plasminogen activator. A major factor for translational failure is likely overwhelming use of young adult rodent models despite the fact that stroke occurs predominantly in aged populations. MicroRNAs (miRs) are non‐coding RNAs that regulate protein translation, and we have previously demonstrated in young adult mice neuroprotection against experimental stroke with anti‐miR‐181a and anti‐miR‐200c. In the present study, to extend translational impact, we tested efficacy of post‐injury intravenous anti‐miR‐181a and anti‐miR‐200c in clinically relevant aged mice.MethodsAll studies were conducted in accordance with National Institutes of Health guidelines for the use of experimental animals, with protocols approved by the Stanford Animal Care and Use Committee. Animal treatment groups were randomized by coin flip, and all analyses were performed by an observer blinded to conditions. Transient focal cerebral ischemia was induced by suture occlusion of the middle cerebral artery (MCAO) for 1h in 20 month‐old male C57BL/6 mice (n=8 per cohort and treatment group). Sham surgery consisted of anesthesia and internal carotid exposure without suture occlusion (n=4 per group). Intravenous infusion: animals were re‐anesthetized and 30 pmol/g anti‐miR‐181a, anti‐miR‐200c or control (MM) in sterile saline (100 μl) was infused over 1 minute into the internal jugular vein at 2h reperfusion. Neurological status was assessed by 4‐point neurologic deficit score at 48h after MCAO. Infarct volume was assessed after sacrifice by anesthesia overdose at 48h after MCAO with triphenyl tetrazolium chloride staining. Infarct volume was calculated as percentage of hemisphere corrected for edema.ResultsMCAO in all groups resulted in significant decreases in neurological score and increased infarct volume relative to sham treated animals. Both anti‐miR‐181a and anti‐miR‐200c treatment resulted in significantly (p<0.05) higher neurological scores and significantly lower infarct volumes relative to MM‐control treated animals. No differences in neurological score or in infarct volume were observed between anti‐miR‐181a and anti‐miR‐200c treatments.ConclusionsBoth anti‐miR‐181a and anti‐miR‐200c are effective non‐invasive post‐stroke interventions to reduce injury in clinically‐relevant aged mice. Future investigations should be extended to testing in aged female cohorts and identifying relevant downstream targets of miR‐181a and miR‐200c.
Antibiotics and High‐Fat‐Diet Induced Gut Inflammation and Impaired Gut Permeability are Improved by Dietary Blueberries Possibly Through NFκB Signaling
Authors: Mattos Della Lucia Ceres , Petersen Chrissa , Adhini Kuppuswamy Satheesh Babu , Pon Velayutham Anandh Babu 
Published: May 2022

BackgroundEvidence indicates that a high fat diet can promote gut inflammation and increase gut permeability. The use of antibiotics further exacerbates these complications and can lead to the development of inflammatory bowel disease. Blueberries are rich in bioactive components such as anthocyanins. We recently reported the vascular and prebiotic effects of dietary blueberries. However, the effects of blueberries on gut inflammation and permeability are unknown. In the present study, we tested the hypothesis that blueberries improve antibiotics and high‐fat‐diet (HFD) induced gut inflammation and impaired gut barrier function in C57BL/6J mice.Methods7‐week‐old male mice (Jackson Lab) consumed standard diet (10% kcal fat) (CON) or HFD (60% kcal fat) with antibiotic cocktail (ampicillin, vancomycin, neomycin sulfate and metronidazole) in drinking water (HFA) or 3.7% freeze‐dried blueberry powder supplemented HFD with antibiotic cocktail in drinking water (HFA+BB) for 12 weeks. Body weight and body composition were assessed at the end of the experiment. Inflammation and permeability of the colon were assessed by the mRNA expression of inflammatory markers (IL‐1β, IL‐6, iNOS, MCP‐1); gut barrier markers (MUC‐2, cldn‐1 and TJP‐10); and markers of NFκB signaling (p65, IKK‐ β and IκBα) by qPCR using specific primers and SYBR green.ResultsHFA mice had an increased body weight, reduced lean body mass, and increased body fat compared to CON mice. Blueberry supplementation did not alter these metabolic parameters in HFA+BB vs HFA mice. mRNA expression of inflammatory markers (IL‐1β, iNOS, MCP‐1); gut barrier marker MUC‐2; and markers of NFκB signaling (p65 and IκBα) were increased in HFA vs CON mice. However, blueberry supplementation improved inflammation and permeability of the colon as shown by a reduced colonic expression of IL‐1β, iNOS, MCP‐1 and MUC‐2 in HFA+BB vs HFA mice. Further, a reduced mRNA expression of p65 and IκBα in HFA+BB vs HFA mice indicates that the protective effect of blueberry on the colon could be mediated through NFκB signaling.ConclusionBlueberry supplementation suppresses colon inflammation and ameliorates colon permeability possibly through NFκB Signaling. Consumption of blueberry is a potential dietary approach to improve gut health.
Effect of Acute Isometric Handgrip Exercise on Vascular Function in Children with Congenital Heart Disease
Authors: Khan Rafique , Boyes Natasha G. , Luchkanych Adam M. S. , Erlandson Marta , Wright Kristi D. , Pockett Charissa , Olver T. Dylan , Tomczak Corey R. 
Published: May 2022

ObjectiveThe reactivity of conduit vessels such as the brachial artery is important in influencing arterial diameter, and subsequently, blood flow. Flow‐mediated dilation (FMD) measures vessel reactivity. The increase in shear stimuli from transient arterial occlusion enhances arterial diameter in an endothelial‐dependent manner, and this is thought to be impaired in individuals with congenital heart disease (CHD). Isometric handgrip (IHG) exercise is a proposed intervention to improve vessel reactivity by optimizing the shear stimuli to provoke changes in arterial diameter. Indeed, IHG training has been found to improve FMD in healthy adults and children. Whether IHG training improves endothelial dysfunction in CHD remains unknown. Improving vessel reactivity in the young becomes increasingly important in optimizing vascular health into adulthood. The effects of acute IHG exercise on the brachial artery were examined in children with CHD.HypothesisWe tested the hypothesis that acute IHG exercise would increase FMD in children with CHD.MethodsFour subjects with CHD (mean, 13 ± 1 year, 3 female) completed a single session of 4 × 2 mins of acute IHG (30% maximum voluntary contraction using the right hand) with 1‐min rest intervals between bouts. Before and after IHG exercise, the right brachial artery was imaged with Duplex ultrasound using a 1‐min baseline, 5 mins of forearm circulatory occlusion, followed by 3 mins of cuff deflation. Blood pressure and heart rate were measured continuously.ResultsPre‐FMD (baseline) mean arterial pressure (pre: 102 ± 17 mmHg vs. post: 110 ± 16 mmHg, p = 0.496) and heart rate (pre: 75 ± 13 bpm vs. post: 66 ± 5 bpm, p = 0.253) were not different. Baseline brachial artery diameter increased following acute IHG in 3 of 4 subjects (pre: 3.11 ± 0.45 mm vs. post: 3.23 ± 0.39 mm, Cohen’s d = 0.3). Peak shear rate was greater post‐IHG in 3 of 4 subjects (pre: 995 ± 346 sec‐1vs. post: 1158 ± 501 sec‐1, Cohen’s d = 0.4). FMD% (4.7% vs. 6.3% and 8.2% vs. 10.5%) and FMD% normalized to shear rate area under the curve (AUC) ratio (2.2E‐5 vs. 7.4E‐5 a.u. and 3.1E‐5 vs. 4.3E‐5 a.u., Cohen’s d = 2.0) increased post‐IHG in 2 of 4 subjects. When brachial artery diameter increased, peak shear rate, FMD%, and FMD% normalized to shear rate AUC improved post‐IHG in 2/3 subjects whereas subject four showed a decrease in brachial artery diameter, FMD% and FMD% normalized to shear rate AUC, with the exception of peak shear rate post‐IHG.ConclusionFavorable changes in brachial artery diameter, peak shear rate, FMD% and FMD% normalized to shear rate AUC following acute IHG may be a promising intervention for improving vascular tone and endothelial function in children with CHD.
Connexin43 Overexpression Exacerbates Myocardial Ischemic Reperfusion Injury in Diabetes via Modulating Cardiac Autophagy
Authors: Liu Danyong , He Jianfeng , Zhou Dongcheng , Chen Jiajia , Zhang Liangqing , Xu Aimin , Xia Zhengyuan 
Published: May 2022

BackgroundPatients with diabetes are more vulnerable to myocardial ischemia/reperfusion injury (MIRI). Abnormal increases of cardiac Connexin43 (Cx43) were shown to be associated with a variety of pathological conditions including myocardial ischemia and diabetic cardiomyopathy, concomitant with various degrees of changes in autophagy. However, the role of Cx43 in MIRI in diabetic conditions and in particular its potential interplay with cardiac autophagy in this pathology is unknown. Thus, the present study was aimed to explore the role and mechanism of Cx43 in diabetic MIRI.Methods and ResultsStreptozotocin (STZ)‐induced diabetic and age‐matched control rats were subjected to MIRI by occluding the left coronary artery for 30 minutes followed by 2 hours of reperfusion at 5 weeks of diabetes induction. In vitro, rat origin H9C2 cardiomyocytes (H9C2) were exposed to 35mmol/L high glucose(HG)for 48 hours(h) in the absence or presence of Cx43 gene knockdown with siRNA, followed by hypoxia for 6h and reoxygenation for 12h. Myocardial infarct size was assessed by TTC staining. Cell viability was detected by the CCK‐8 assay, apoptosis by TUNEL assay. Cardiac Cx43 protein, apoptosis‐related proteins and autophagy‐related LC3, p62 and mTOR proteins were assessed by Western blotting. Post‐ischemic myocardial infarct size and cardiac CX43 protein expression were significantly increased in diabetic rats as compared with that in the control (p<0.05), concomitant with increases in the ratio of LC3 II/I and in the protein expression of P62 and mTOR (all p<0.05). In vitro, exposure of H9C2 cells to HG significantly increased cell injury evidenced by increased LDH release and reduced cell viability, and significantly enhanced cell apoptosis and reactive oxygen species(ROS) production that was accompanied by increased cardiomyocyte CX43 overexpression and enhanced autophagy but paradoxically also enhanced mTOR activation, similar to that seen in vivo. All these changes were further exacerbated following H/R under HG. Cx43 Knockdown in H9C2 results in decreased ROS production and decreased apoptosis after H/R under HG leading to increased cell viability (all p<0.05), while Cx43 knockdown attenuated autophagy. Application of the selective mTOR inhibitor rapamycin abolished the abovementioned beneficial effects of Cx43 Knockdown.ConclusionOverexpressed CX43 in the diabetic heart exacerbates MIRI in diabetes through enhanced cardiac autophagy under hyperglycemic condition.
Primary cilia control kidney inflammation and scarring in response to obstruction
Authors: Aka Amandine , Viau Amandine , Quatredeniers Marceau , Terzi Fabiola , Bienaimé Frank 
Published: May 2022

Primary cilium is a unique antenna‐like structure that protrudes from the surface of most mammalian cells. Primary cilia are located at the apical surface of renal tubular epithelial cells, where they are bathed in the forming urine. Overall, primary cilia are signaling platforms that integrate mechanical and chemical cues. Yet, the functions of tubular cells cilia in kidney physiology remain unclear. Mutations in genes encoding ciliary proteins frequently lead to the development of chronic kidney diseases such as Autosomal Dominant Polycystic Kidney Disease or Nephronophthisis. A common denominator of these “renal ciliopathies” is the infiltration of the kidney by immune cells and myofibroblasts that prompt renal scarring. In the absence of mutations, such events can notably be triggered by tubular obstruction, which abolished urinary flux and therefore may affect cilia signaling. Yet the contribution of primary cilia in kidney response to obstruction is unknown.Here, we combined comparative analysis of kidney gene expression datasets, models of mechanical tubular obstruction and genetic ablation of primary cilia to explore this question. Our results indicate that the renal cytokine landscape of ciliopathies massively overlaps with the one induced by ureteral obstruction. Applying this latter model to mice with tubule specific cilia ablation, we demonstrated that cilia are instrumental in the induction of most of these cytokines. Subsequently cilia ablation mitigated macrophage and neutrophil recruitment to the kidney and reduced fibrosis burden.All together, these results show that primary cilia evoke a coordinated response to tubular obstruction reminiscent of genetic renal ciliopathies. Elucidating the mechanisms underlying this function of primary cilia may illuminate the pathophysiology of both genetic and non‐genetic chronic kidney diseases.AA* and AV* these authors equally contributed to this work
Multiplex Mass Spectrometry for Enzymatic Activities Screening of Lysosomal Storage Diseases
Authors: Jayaweera Taniya , Darie Ion Laura , Petre Brindusa‐Alina , Darie Costel 
Published: May 2022

Lysosomal storage diseases (LSDs) are a group of rare and inherited disorders of lysosome function and they are classified into more than 50 types (e.g., mucopolysaccharidoses, neuronal ceroid lipofuscinoses, Fabry’s Disease; Pompe Disease, etc.). The majority of LSDs result from defective lysosomal enzyme activity leading to accumulation of endogenous macromolecules in the lysosome causing severe disease symptoms and finally death. For some LSDs, treatment is available in the form of enzyme replacement therapy with good results if the therapy is started as soon as possible, making the diagnosis of crucial importance. State of art now in LSDs diagnostic employs in first stage, enzymatic determinations by fluorimetry or by mass spectrometry (in few cases).In this report, we describe a highly specific and sensitive diagnostics on dry blood spots (DBSs) for (i) molecular determinations of LSDs, particularly mucopolysaccharidoses (MPSs) and neuronal ceroid lipofuscinoses (NCLs), by simultaneous fluorimetric and mass spectrometric analysis using new types of substrate derivatives based on different alkyl‐umbelliferone; (ii) clinical diagnostics of LSDs by multiplex‐MS‐MRM analysis using new type of substrate derivatives and (iii) clinical validation of the new developed methods using DBS samples for patients with established LSDs. We have developed a high‐throughput single and multiplexing assay for rare diseases (e.g. MPS 1, MPS 2, MPS 6, NCL 2, NCL 10, Fabry Disease, etc.) in DBSs. A common substrate for the fluorimetric measurement of a lysosomal enzyme activity is a molecule with 2 different parts which are bound covalently: a group recognized by the target enzyme (e.g. sugar, lipid) and 4‐umbelliferone and the product resulted after the enzymatic reaction is always 4‐methyl umbelliferone. In our tests, the enzymatic activity levels in DBSs were determinate by fluorimetry or multiple reactions monitoring mass spectrometry in the presence of an internal standard showing a good statistical correlation in singles assays. Moreover, we developed duplex and triplex assays for the diagnosis of different LSDs from the muccopolysacharidoses family using modified substrates based on different coumarin derivates obtained through Pechman condensation. The new umbelliferone derivatives were synthesize by substituting groups in position 4 and 7 of the alpha‐ coumarin molecule with others e.g. 4‐ ethyl‐ umbelliferone, 4‐propyl‐umbelliferone, etc.In conclusion, by quantification of umbelliferone derivatives as products of enzymatic reactions either by fluorimetry or mass spectrometry, the newly proposed substrates can be easily use for clinical diagnosis of several LSDs.
Development of a Dietary and Life‐style algorithm for Prophylactic‐Remission of IBS: A Case Study
Authors: Shujaat Tayyaba , Malik Samina 
Published: May 2022

Inflammatory Bowel Disease is considered incurable in allopathy. Medical professionals hardly advise nutritive‐therapy or life‐style management. This adds to the prevalence of chronic illness and may end into carcinoma. This case study is a success‐story of a young student at 24 years of age who was diagnosed with IBS on colonoscopy. The only medicine advised was hydrocortisone‐enema which did not benefit her. Stress related to father’s demise and unhealthy‐lifestyle and diet were the identified precipitating factors. History included off and on constipation, bloody‐motion with mucus discharge, pain‐free defecation, gaseous‐abdomen with bloating and dull‐pain. Life‐style behavior included poor physical activity, disturbed sleep‐wake cycle, compromised hostel diet and academic‐deadlines related stress.The impact of Dietary variation was monitored in terms of variation in clinical features. Flare was observed with red‐beans, chick‐peas and black‐lentil. Gluten and Lactose intolerance were ruled out by diet‐variation. Probiotic‐treatment and low FODMAP diet helped in remission. The specific algorithm that facilitated in recovery included figs, strawberries, cranberries, pomegranate, Salmon fish, Greek‐yogurt, olive‐oil, oatmeal, walnuts, dates and green‐leafy‐vegetables. Life‐style modification included mindfulness meditation, walking/jogging, soul‐cycling and counselling. Outcome was measured and compared. Remission was achieved within 4‐5 months and the patient is recovered since last 1.5 years as evidenced by laboratory data. It includes CRP reduction within normal range, hemoglobin improvement (10.2 to 12.2 g/dl), MCV improvement (73 to 86.9 fL), MCH improvement (21.2 to 27.5 pg), MCHC improvement (29.1 to 31.7 g/dl), HCT improvement from 35% to 38.5%, Fecal Calprotectin reduction from 712.9 to 415.3 µg/g and total protein reduction from 8.39 to 7.48 g/dl. Hopefully continuous alternate treatment may normalize the calprotectin marker as well.
Outcome of short‐term physiotherapy intervention program on early stage of multiple sclerosis ‐ A case report
Authors: Nandennagari Sailaja , Preethi Annam , Bethala Krupavarm 
Published: May 2022

INTRODUCTIONMultiple sclerosis is a chronic autoimmune progressive disease of demyelination of central nervous system with subsequent axonal damage. The symptoms are due to central nervous system lesions resulting from loss of oligodendrocytes, which myelinates CNS leading to tingling and numbness of limbs and reactive gliosis with no cure for the disease. But CNS diseased effects are often controlled through rehabilitation.OBJECTIVE OF THE STUDYThe aim of this study is to observe the importance of early physiotherapy rehabilitation along with immunosuppressants to suppress and reduce the symptoms and slows down the disease process beginning from the initial day of hospitalization to six weeks which causes progression in the patient reducing the incapacity and improves functional measures and quality of life in multiple sclerosis patients. Muscle weakness, and spasticity, balance and coordination can be improved through stretching and strengthening exercises.METHODPatient strictly followed intervention for a period of six weeks under the supervision of Physiotherapist. Intervention includes strengthening, aerobic conditioning, flexibility exercises, coordination exercise, balance exercises, gait training using assistive devices, sensory, functional, bowel and bladder control training. Interventions were gradually progressed up to the patient every week according to their symptoms. Patient was assessed in 1st and 7th week using the outcome measures namely Functional independence measure (FIM) and Short Form survey‐12 (SF‐12) assessing the impact of health on patient’s everyday quality of life.RESULTSAfter the 7th week re‐assessment, it has been shown there is a difference in the value of outcome measures. FIM level has improved from 3‐moderate assistance with helper to 6‐modified independence without helper. SF‐12 physical score showed marked improvement from 48.020307 to 56.57706 while SF‐12 mental score change showed very minor change.CONCLUSIONMultiple sclerosis disease impairment is primarily a consequence of disease progress, but it can be aggravated by reduced physical activity leading to muscle weakness, decreased ROM, spasticity. Exercise and training have been shown to improve the above said deteriorations in multiple sclerosis patients and certainly can be alleviated.Score through FIM and Health survey scale are tabulated as follows

Outcome measure
Preintervention
Postintervention

FIM, Functional Independent Measure (in scales)
3‐‐ Moderate Assistance(>= 50%): Helper‐Modified Dependance
6‐‐ Modified, Independence (Device): No Helper

SF‐12, Quality of life measure
PCS‐12 (Physical Score): 48.020307 MCS‐12 (Mental Score): 59.04606
PCS‐12 (Physical Score): 56.57706 MCS‐12 (Mental Score): 60.75781
Aging Alters Integrin‐mediated Vascular Smooth Muscle Function in Soleus Feed Arteries
Authors: Shin Song Yi , Ojha Krishna R. , Padgham Samuel , Trache Andreea , Woodman Christopher 
Published: May 2022

IntroductionPrevious data have shown that aging impairs vasomotor function and alters vascular smooth muscle cell (VSMC) properties. Integrins play an important role in regulating many cellular functions including arterial contractility. However, how aging affects integrin function, and their contribution to impaired constriction in aged arteries has not yet been elucidated. Thus, the purpose of this study was to investigate the age‐induced alteration of integrin function in isolated VSMC and in intact soleus muscle resistance arteries.MethodsSoleus muscle feed arteries (SFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats, cannulated with glass micropipettes and pressurized at 90cm H2O. Endothelial cells were removed (denuded) by passing 5 ml of air through the artery lumen. Vasoconstrictor responses were assessed by adding of norepinephrine (NE; 10‐9‐10‐4M), angiotensin II (Ang II; 10‐11‐10‐7 M), or phenylephrine (PE; 10‐9‐10‐4 M) in the presence or absence of RGD, an integrin inhibitory peptide. RGE, a non‐inhibitory peptide was used as control. To investigate changes in integrin expression and recruitment at focal adhesions with age, RT‐qPCR, cell adhesion assays, and total internal reflection fluorescence (TIRF) imaging were performed using VSMC isolated from young and old SFA.ResultsOld denuded SFA had reduced vasoconstrictor responses to NE, PE, and Ang II. In the presence of the RGD‐inhibitory peptide, constrictor responses to Ang II were significantly inhibited in denuded old vs. young SFA. Constrictor responses to NE and PE were not significantly altered by RGD. Constrictor responses to NE, PE, and Ang II were also not affected by RGE. Gene expression of specific integrins expressed by VSMC were downregulated in old VSMC compared to young. In addition, RGD‐treated VSMC showed decreased adhesion to fibronectin in both young and old VSMC compared to RGE non‐inhibitory peptide. Quantitative analysis of TIRF images showed that recruitment of integrin α5 and β3 was diminished in old VSMC while β1 was not altered with age.ConclusionsTaken together, these data suggest that aging leads to integrin dysfunction, which contributes to decreased contractile properties of vascular smooth muscle in SFA.