Beta Alpha Research Articles

Costunolide, an effective agent against oxidative damage, apoptosis and autophagy in the ovarian torsion/detorsion model

Aim This study assessed the efficacy of costunolide (COST) against oxidative tissue damage in the ovarian torsion/detorsion (TD) model. Methodology Animals were randomly assigned to sham, ovarian TD, COST 5 mg/kg + ovarian TD, and COST 10 mg/kg + ovarian TD groups. COST’s effectiveness was determined by assessing oxidative stress markers, interleukin levels, and histopathological examinations. Results Oxidative stress markers were elevated in the ovarian TD group compared to the sham group. COST treatment represented a decline compared to the TD group. Besides, the antioxidant activity was significantly higher in the ovarian TD group than in the sham group. COST treatment improved the antioxidant parameters compared to the TD group. Inflammatory parameters, such as tumour necrosis factor- alpha (TNF-α) and interleukin 1-beta (IL-1β) were higher in the ovarian TD group than the sham group. Conclusion COST treatment suppressed the proinflammatory cytokine expression compared to the TD group. Histopathological data supported these findings.

HOMOCYSTEINE AS A RISK FACTOR FOR CARDIOVASCULAR DISEASES IN PATIENTS WITH END-STAGE RENAL DISEASE

Cardiovascular diseases (CVD) still remain the main cause of mortality in patients with chronic renal failure in the final stage (chronic terminal renal insufficiency- ESRD), which appears as a consequence of premature atherosclerotic processes (atherosclerosis praecox). In addition to known factors such as: diabetes, arterial hypertension, sedentarity, uremic dyslipidemia, obesity, oxidative stress, MIA syndrome, increased proinflammatory cytokines (interleukin 6, Interleukin 18, Interleukin-1 beta (IL-1β) alpha necrosis factor (alpha tumor necrosis factor (IL-1α) [1] in recent years as an independent non-traditional risk factor for the occurrence of CVD in patients with chronic renal failure and those with ESRD (uraemic) treated with chronic hemodialysis (HD) is also homocysteine (Hcy ) with its high concentrations - hyperhomocysteinemia (HHcy). In recent years, a large number of studies suggest that high levels of Hcy are an important biomarker for the risk of CVD, the increased level of Hcy significantly increases the impact on CVD and mortality in this population (2,3). Therefore, it is necessary to evaluate the level of Hcy in patients with ESRD from the initial stages in order to prevent the occurrence of premature atherosclerotic processes that lead to the risk of CVD.

Extracellular matrix composition analysis of human articular cartilage for the development of organ-on-a-chip

IntroductionArticular cartilage has a complex extracellular matrix (ECM) that provides it a defined architecture for its load-bearing properties. The complete understanding of ECM components is imperative for developing biomimetic organ-on-a-chip tissue construct. ObjectiveThis study aimed to decellularize and characterize the ECM for its protein profiling to generate a niche for enhanced chondrocyte proliferation. MethodsArticular cartilage scrapings were subjected to mechanical and collagenase digestion, followed by sodium dodecyl sulfate (SDS) treatment for 8 h and 16 h. The de-cellularization efficiency was confirmed by hematoxylin & eosin, alcian blue, masson's trichrome staining, and scanning electron microscopy (SEM). The ECM protein profile was quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS) using a bottom–up approach. ResultsHistological characterization revealed void lacunae that lacked staining for cellular components. The ECM, sulfated glycosaminoglycan content, and collagen fibers were preserved after 8 h and 16 h of de-cellularization. The SEM ultrastructure images showed that few chondrocytes adhered to the ECM after 8 h and cell–free ECM after 16 h of de-cellularization. LC-MS/MS analysis identified 66 proteins with heterotypic collagen types COL1A1-COL6A1, COL14A1, COL22A1 and COL25A1 showed moderate fold change and expression levels, while COL18A1, COL26A1, chondroitin sulfate, matrix metalloproteinase-9 (MMP9), fibronectin, platelet glycoprotein 1 beta alpha (GP1BA), vimentin, bone morphogenetic protein 6 (BMP6), fibroblast growth factor 4 (FGF4) and growth hormone receptor (GHR) showed maximum fold change and expression levels. ConclusionsThe standardized de-cellularization process could preserve majority of ECM components, providing structural integrity and architecture to the ECM. The Identified proteins quantified for their expression levels provided insight into engineering the ECM composition for developing cartilage-on-a-chip.

White Coat Effect: Is It Because of the Hospital Setting, or Is It Physician-Induced?

White coat hypertension (WCH) patients are those individuals who have high blood pressure (BP) in the medical environment but are normal during their daily activities. White coat hypertensive patients with normal daytime ambulatory blood pressure monitoring (ABPM) rapidly progress to sustained hypertension. WCH is mainly treated with non-pharmacological methods. Alpha-1 agonists and beta blockers are logical treatment choices for patients with fixed hypertension with the White Coat Effect (WCE). Masked hypertension patients are those individuals who have normal values at the doctor's office but elevated BP at home or during 24-hour ABPM (24-hour or daytime). ABPM is a more practical and reliable method for detecting patients with WCH. This observational study was conducted at Dayanand Medical College & Hospital, Ludhiana, over the course of one year (December 2015 to November 2016). The primary objective of the study was to determine whether there was a difference in blood pressure readings between the home setting and the hospital setting. The secondary objective was to determine whether the difference, if present, between the hospital and home readings was due to the hospital setting, physician presence, or a combination of both. Patients with stage 1 hypertension were included in the study, irrespective of antihypertensive treatment. Patients with ischemic heart disease, chronic liver failure, and chronic kidney disease who could not follow protocol instructions were excluded. In our study, the mean age of patients was 53.91±12.86 years. The patient's mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings at the hospital were higher than their home readings (p-0.012; p-0.001, respectively). Mean hospital SBP and DBP readings recorded by the physician were higher than readings recorded by patients alone at home (p-0.002; p-0.014, respectively) and alone at the hospital (p-0.004; p-0.001, respectively). BP readings taken by the physician with a manual sphygmomanometer were significantly lower than those taken with a digital sphygmomanometer by patients and physicians in all settings (p<0.05). The mean rise in BP was significant in both the physician's presence and the hospital environment (p<0.05 for both), and this rise was more significantly associated with the hospital effect than the physician effect (p<0.05). Misdiagnosis of hypertension results in inappropriate prescription and overuse of antihypertensive medications for individuals who are not persistently hypertensive. So it is very important to rule out WCH in both the hospital setting and the physician's presence, more precisely by ABPM. WCH can be diagnosed with regular BP monitoring by a digital sphygmomanometer at home.

تأثير الرش بتركيزات مختلفة من المستخلص المائي لفصوص الثوم في صفات النمو الزهري والمحصول لنبات الخيار (.Cucumis sativus L) صنف (Beit Alpha) تحت الظروف المناخية لمدينة إب في اليمن

الملخص يعدّ محصول الخيار من محاصيل الخُضر المنتشرة زراعته محلياً بشكل واسع في البيوت المحمية، نظراً إلى القيمة الغذائية لثماره. لكنه يعاني من أن عدد الأزهار المذكرة في النبات الواحد أعلى من عدد الأزهار المؤنثة؛ مما يؤثر سلبياً في إنتاج النبات الواحد، لذلك أُجري البحث بهدف دراسة تأثير الرش بتركيزات مختلفة من المستخلص المائي لفصوص الثوم (1.25، 2.50، 3.75، 5، 6.25، 7.50 سم3/ لتر، إضافة إلى استخدام الماء المقطر كشاهد) في صفات النمو الزهري والمحصول الكلي لنبات الخيار، صنف بيت ألفا، في عام 2019؛ بغرض زيادة عدد الأزهار المؤنثة والمحصول للنبات الواحد. نُفذ البحث في المشتل التابع لمكتب الزراعة والري في محافظة إب في الجمهورية اليمنية، ودُرست مجموعة من صفات النمو الزهري والمحصول. وأظهرت النتائج أن الرش بالمستخلص المائي لفصوص الثوم أدى إلى تحسين صفات النمو الزهري والمحصول الكلي؛ إذ أعطى التركيز 3.75 سم3/ لتر أعلى القيم وبتفوق معنوي للصفات المدروسة (عدد الأزهار المؤنثة/ نبات، والنسبة الجنسية والإنتاجية الكلية) بلغت 40.10 زهرة/ نبات، في حين بلغت الصفتان المدروستان الأخرييان 1.29 و31.44 طناً/ هكتار على التوالي، عدا موقع أول زهرة أنثوية وعدد الأزهار المذكرة/ نبات؛ وقد أعطى التركيز نفسه أقل القيم وبانخفاض معنوي بلغت 4.98 و30.82 زهرة على التوالي، بينما التركيز 5 سم3/ لتر أعطى أعلى القيم للنسبة المئوية للثمار العاقدة وبتفوق معنوي بلغت 58.11%. تم تحسين قيمة الانحدار التربيعي (R2) من 3.6% (خطي) إلى 86.6% (تربيعي)، ويلاحظ أن الانحدار في صورة المنحنى التربيعي أظهر كفاءة أعلى عن الصورة في المنحنى الخطي في تفسير نقص أو زيادة الإنتاج المرتبط بنقص أو زيادة تركيزات مستخلص فصوص الثوم. وفي المنحنى التربيعي، إذا تم رش مستخلص الثوم الورقي بمستوى 3.53 سم3/ لتر، فمن المتوقع أن يكون الحد الأقصى لإجمالي محصول الخيار 30.94 طناً/ هكتار.أثبت البحث فاعلية مستخلص فصوص الثوم عند تركيز معيّن في رفع أعداد الأزهار المؤنثة مقارنة بالأزهار المذكرة في النبات الواحد ومما ينتج منه زيادة إنتاج النبات.

Hannah Claire Haines, 1891–1974: Not the Average “Militant Female”

Hannah Claire Haines, 1891–1974: Not the Average “Militant Female”

Development and In-Vitro Evaluation of Plantago ovata Based Rapid Disintegrating Tablets of Labetalol Hydrochloride

Objectives: To avoid swallowing problems of conventional tablets and improved patient compliance Plantago Ovata based Labetalol HCl Rapid disintegrating tablets have been prepared. Methods: Six different (F1 to F6) batches of Labetalol HCl Rapid disintegrating tablets were developed by ‘direct compression method’ using Plantago ovata as a natural super-disintegrating agent. The formulated RDT were tested for angle of repose’, densities like tapped and bulk density, Hausner’s ratio, Carr’s index like pre-compression parameters and for thickness, weight variation or weight uniformity, tablet hardness, % drug content or content uniformity, water absorption ratio’, time require for wetting of tablets’ means wetting time, in-vitro drug disintegration time and in-vitro drug dissolution studies under post-compression parameters of evaluation. Results: It was found that the all the results of these pre-compression and post-compression parameters comply with official standards. The drug release was determined using dissolution media of pH 6.8 phosphate buffer through in-vitro dissolution of drug. This study showed that a rapid drug release by prepared tablets. The optimized formulation F6 showed higher water absorption ratio`, lower wetting time, minimum in-vitro disintegration time’ and higher drug release amongst all the formulations. The F6 formulation was considered the best among all formulations. Conclusion: The prepared rapid disintegrating tablets shows rapid onset of action by quick drug release, minimize side effects and enhanced patient compliance. These prepared tablets containing selective alpha-1 and non-selective beta adrenergic antagonist’ drug candidate Labetalol HCl, will be very useful in the treatment of high blood pressure with enhanced bioavailability.&#x0D; Keywords: Rapid disintegrating tablets, Labetalol Hydrochloride, Bioavailability Enhancement, Natural Superdisintegrant, Plantago Ovata, High Blood Pressure, RDT, Patient Compliance

1465-P: Metabolic Remodeling in Pancreatic Beta Cells in Japanese Patients with Type 2 Diabetes

Background and Aims: It has been shown that metabolic remodeling from oxidative phosphorylation to glycolysis via activation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) occurs in pancreatic beta cells in non-Asians with diabetes, resulting in impaired beta cell function. We used multiple autopsy pancreatic sections to investigate whether such changes occur in Japanese patients with type 2 diabetes (T2D) , and if so, which clinical and pathological features of islets relate to this remodeling. Methods: Autopsy pancreatic sections from patients with T2D and non-diabetic donors (ND) were stained with antibodies against PFKFB3, insulin, and glucagon. The PFKFB3-positive ratio of pancreatic beta cells and alpha cells between T2D and ND were compared. Next, the relationships between PFKFB3-postive beta cell ratio, patient background factors and pathological features of the islets were explored. Results: In total, 36 cases (18 cases each for T2D and ND) were enrolled and 50-100 islets/case were evaluated. Mean age was 70.6 ± 7.7 vs. 64.3 ± 12.8 years and body mass index (BMI) 22.4 ± 4.2 vs. 23.3 ± 4.5 kg/m2, respectively. T2D duration was 9.8 ± 9.9 years. The PFKFB3-positive beta cell ratio was significantly higher in T2D (29.7 ± 18.6% vs. 11.1 ± 8.7%, p&amp;lt;0.05) , whereas the PFKFB3-positive alpha cell ratio did not differ between groups. A negative correlation between PFKFB3-positive beta cell ratio and BMI was found only in the T2D group (r=-0.65, p&amp;lt;0.05) . No correlation was observed between PFKFB3-positive beta cell ratio and age/disease duration in the T2D group. Thioflavin T staining revealed a positive correlation between amyloid deposition in the islets of T2D and PFKFB3 positivity in beta cells (r=0.67, p&amp;lt;0.05) . Conclusion: Our results indicate that intracellular metabolic remodeling mediated by upregulation of PFKFB3 occurs in pancreatic beta cells of Japanese patients with T2D. Low BMI and amyloid deposition may affect PFKFB3 expression in beta cells from patients with T2D. Disclosure R.Izumihara: None. H.Nomoto: None. K.Chiba: Research Support; Grant for Young Researcher from Japan Association for Diabetes Education and Care, Japan Diabetes Society Junior Scientist Development Grant, Japan Society for the Promotion of Science , MSD Life Science Foundation, Promotion for Young Research Talent and Network, The Akiyama Life Science Foundation, The Uehara Memorial Foundation. H.Kameda: None. K.Cho: None. A.Nakamura: Research Support; Kissei Pharmaceutical Co., Ltd., MSD, Nippon Boehringer Ingelheim, Taisho Pharmaceutical Holdings Co., Ltd. H.Miyoshi: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Company, Ltd., LifeScan, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Speaker's Bureau; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kowa Company, Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. H.Mizukami: None. T.Atsumi: Consultant; AbbVie Inc., AstraZeneca, MEDICAL &amp; BIOLOGICAL LABORATORIES CO., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Research Support; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Speaker's Bureau; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, UCB, Inc. Funding JSPS KAKENHI Grant Number JP20281167.Japan Diabetes Society Junior Scientist Development Grant.MSD Life Science Foundation, Public Interest Incorporated Foundation.

Potential cardioprotective influence of bupropion against CCl4-triggered cirrhotic cardiomyopathy

Bupropion, an atypical anti-depressant and smoking cessation aid, attenuates complications arising from the activation of inflammatory and oxidative pathways. In this study, the effect of bupropion on an inflammatory and oxidative condition induced by carbon tetrachloride (CCl 4 ) namely cirrhotic cardiomyopathy (CCM) was investigated in rats. CCM was induced by intraperitoneal injection of CCl 4 (0.4 g/kg, i.p.). Bupropion was treated orally at doses 30 and 60 (mg/kg, p.o.) for 8 weeks. CCl 4 treatment significantly lowered hepatic antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) while enhanced Malondialdehyde (MDA). Elevations in serum nitric oxide (NO) metabolites nitrite/nitrate, and cardiac tumor necrosis factor alpha (TNF-α) and interleukin 1-beta (IL-1β) levels were observed. Cirrhosis also decreased contractility in response to isoproterenol (10 −10 to 10 −5 M). The spleen weight and intrasplenic pressure increased and QTc, QRS and RR intervals prolonged. Pathological damages in the liver for example focal necrosis, fibrosis and the hepatic blocking increased. On the other hand, bupropion increased GSH, CAT and SOD and lowered MDA. Bupropion reduced NO metabolites and TNF-α levels and decreased IL-1β. The cardiac contractile force improved at maximal effect (Rmax) 10 -5 M by bupropion. The intrasplenic pressure was reduced by bupropion. Bupropion reduces QTc, QRS and RR intervals and the liver tissue damages. Bupropion played a cardioprotective role reducing inflammatory and oxidative factors. It may recover the impairment of cardiac contractility and hyperdynamic condition in CCM, and this effect could be mediated at least in part by a NO-dependent mechanism.

Umuhengerin Neuroprotective Effects in Streptozotocin-Induced Alzheimer's Disease Mouse Model via Targeting Nrf2 and NF-Kβ Signaling Cascades.

Alzheimer’s disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD (SAD) associated neuropathological changes. The present study was undertaken to explore the neuroprotective effects of the methoxy flavonoid, umuhengerin, in an STZ-induced SAD mouse model as a potential therapy for AD. Mice were injected once with STZ (3 mg/kg, ICV), followed by daily administration of umuhengerin (orally, 30 mg/kg) or the positive control donepezil (orally, 2.5 mg/kg) for 21 days. The pharmacological activity of umuhengerin was assessed through estimation of oxidative stress and inflammatory markers via mouse ELISA kits, Western blot analysis, and brain histopathological examination. Morris water maze test was also conducted to investigate umuhengerin-induced cognitive enhancement. The results showed that umuhengerin attenuated STZ-produced neuroinflammation and oxidative stress with a notable rise in the expression of Nrf2 (nuclear factor erythroid 2-related factor 2). In contrast, it downregulated Keap-1 (Kelch-like ECH associated protein 1), as well as elevated brain contents of GSH (reduced glutathione) and HO-1 (heme oxygenase-1). STZ-injected animals receiving umuhengerin showed marked downregulation of the nuclear factor kappa beta (NF-Kβp65) and noticeable increment in the expression of its inhibitor kappa beta alpha protein (IKβα), as well as prominent reduction in malondialdehyde (MDA), H2O2 (hydrogen peroxide), and TNF-α (tumor-necrosis factor-alpha) contents. Β-secretase protein expression and acetylcholinesterase (AchE) activity were also diminished upon umuhengerin injection in the STZ group, leading to decreased Aβ formation and cognitive improvement, respectively. In conclusion, umuhengerin neuroprotective effects were comparable to the standard drug donepezil; thus, it could be an alternative approach for AD management.

Protective effect of Palmijihwanghwan in a mouse model of cigarette smoke and lipopolysaccharide-induced chronic obstructive pulmonary disease

BackgroundPalmijihwanghwan (PJH) is a traditional medicine and eight constituents derived from PJH possess anti-inflammatory activities. However, the scientific evidence for its potential as a therapeutic agent for inflammatory lung disease has not yet been studied. In this study, we examined the protective effect of PJH in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) with lipopolysaccharide (LPS).MethodsMice received CS exposure for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. PJH (100 and 200 mg/kg) was administrated daily 1 h before CS treatment for the last 4 weeks.ResultsCompared with CS plus LPS-exposed mice, mice in the PJH-treated group showed significantly decreased inflammatory cells count and reduced inflammatory cytokines including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) levels in broncho-alveolar lavage fluid (BALF) and lung tissue. PJH also suppressed the phosphorylation of nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) caused by CS plus LPS exposure. Furthermore, CS plus LPS induced increases in matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-β (TGF-β) expression and collagen deposition that were inhibited in PJH-treated mice.ConclusionsThis study demonstrates that PJH prevents respiratory inflammation and airway remodeling caused by CS with LPS exposure suggesting potential therapy for the treatment of COPD.

GC-MS/FID analysis, antibacterial activity and modes of action of essential oils from three Aframomum species found in Cameroon against foodborne pathogenic bacteria

Background: The current study examined the chemical profile and in vitro antibacterial activity of essential oils (EOs) extracted from Aframomum danielli (leaves and seeds), Aframomum chlamydentum (leaves), and Aframomum melegueta (leaves) against foodborne pathogenic bacteria.&#x0D; Methods: The hydro-distillation technique using a Clevenger-type apparatus was used to extract EOs, whereas the Gas Chromatography-Mass Spectrometry (GC-MS) and GC coupled to Flame Ionization Detector (GC-FID) allowed the chemical characterization of oil constituents. The broth micro-dilution method was applied for the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Besides, some modes of action were studied on the cell membrane integrity and biofilm formation of Salmonella typhi.&#x0D; Results: The major compounds identified from EOs of A. danielli seeds were eucalyptol (48.707%), limonene (11.368%), beta pinene (10.342-10.335%), and alpha terpineol (8.785-9.049%), whereas EOs from A. danielli leaves were dominated by sabinene (42.87%), beta pinene, (11.22%), caryophyllene (7.84%), terpinen-4-ol (5.68%), linalool (3.48%) and gamma terpinene (2.02%). Major volatile markers from EOs of A. chlamydentum leaves comprised beta pinene (49.72%), caryophyllene (10.62%), alpha pinene (6.21%) and linalool (2.96%), while those of EOs from A. melegueta included beta pinene (37.15%), caryophyllene (17.64%), caryophyllene oxide (8.72%) and alpha pinene (8.26%). This study is the first to report on the chemical constituents of EOs from A. chlamydentum. Test oils displayed significant antibacterial activity with the MIC ranging from 0.0625 to 0.5% (v/v). EOs from A. melegueta (leaves) appeared to be the most active, acting against all tested bacteria. All EOs identified displayed bactericidal effects against Citrobacter freundii, a bacterium known to cause a broad range of infections associated with a higher rate of in-hospital mortality. The EOs from A. melegueta may act through perturbation of cell membrane integrity and permeability as well as the inhibition of bacterial biofilm formation.&#x0D; Conclusion: Our findings suggest the possible application of essential oils in agricultural food products for the control of bacterial diseases.

Single cell transcriptomics reveal trans-differentiation of pancreatic beta cells following inactivation of the TFIID subunit Taf4

Regulation of gene expression involves a complex and dynamic dialogue between transcription factors, chromatin remodelling and modification complexes and the basal transcription machinery. To address the function of the Taf4 subunit of general transcription factor TFIID in the regulation of insulin signalling, it was inactivated in adult murine pancreatic beta cells. Taf4 inactivation impacted the expression of critical genes involved in beta-cell function leading to increased glycaemia, lowered plasma insulin levels and defective glucose-stimulated insulin secretion. One week after Taf4-loss, single-cell RNA-seq revealed cells with mixed beta cell, alpha and/or delta cell identities as well as a beta cell population trans-differentiating into alpha-like cells. Computational analysis of single-cell RNA-seq defines how known critical beta cell and alpha cell determinants may act in combination with additional transcription factors and the NuRF chromatin remodelling complex to promote beta cell trans-differentiation.

A role of noradrenergic receptors in anxiolytic-like effect of high CRF in the rat frontal cortex

Corticotropin releasing factor (CRF) is a neuropeptide widely distributed in the brain as a hormonal modulator and neurotransmitter. The best known behavioral function of CRF is activation of stress and anxiety via the hypothalamus and limbic structures but the role of CRF in the cortex is still poorly understood. Our previous studies have shown anxiolytic-like effects of high doses of CRF injected into the Fr2 frontal cortex and involvement of CRF1 receptors (R) in that effect. These results seemed to be controversial as most other studies suggested anxiogenic and not anxiolytic effects of CRF1R stimulation. Since stress is associated with adrenergic system, in the present study, we focused on participation of alpha1 and alpha2 or beta adrenergic receptors in the anxiolytic-like effect of CRF. Moreover, we verified whether these effects of CRF in the Fr2 were really connected with CRF1R.Male Wistar rats were bilaterally microinjected with CRF in a dose of 0.2 μg/1 μl/site or with the specific agonist of CRF1R, stressin 1 (0.2–0.0125 μg/1 μl/site) into the Fr2 area. The elevated plus maze (EPM) test was performed 30 min later to assess the anxiolysis. An involvement of noradrenergic receptors in the CRF induced anxiolytic-like effect in the Fr2 was studied by pretreatment with the alpha1 antagonist prazosin, alpha2 agonist clonidine, alpha2 antagonist RS 79948 or beta antagonist propranolol, 20–30 min before CRF. The influence on anxiety was assessed in the EPM test. The results show that anxiolytic behavior after CRF microinjection into the Fr2 area seems to be mainly connected with the CRF1R activation because a similar effect was observed after stressin 1 administration and it was blocked by CRF1R antagonist. The results observed after administration of noradrenergic ligands indicated that anxiolytic effects of CRF in the Fr2 engaged the alpha1 and alpha2 adrenergic receptors but not beta receptors.

Erratum for “Effect of aqueous leaf extract of Thunbergia laurifolia on alcohol-induced liver injury in rats”

Purpose: To investigate the antioxidant and anti-inflammatory effects of aqueous leaf extract of T. laurifolia against alcoholic liver injury in rats.&#x0D; Methods: Male Wistar rats were administered either normal saline, ethanol (EtOH), normal saline with low or high dose T. laurifolia leaf extract (TL-LD or TL-HD), EtOH with TL-LD or EtOH with TL-HD. Blood biochemical indices: hepatic malondialdehyde (MDA) levels, liver histopathology, hepatic cytochrome P450 2E1 (CYP2E1), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and proinflammatory cytokines, including interleukin 1 beta (IL-1β) and tumor necrotic factor alpha (TNF-α) mRNA expressions, were determined using standard methods.&#x0D; Results: The leaf extract of T. Laurifolia decreased hepatic MDA levels, improved liver pathology and down-regulated mRNA expressions of CYP2E1, NADPH oxidase and pro-inflammatory cytokinesin ethanol-treated rats.&#x0D; Conclusion: These results demonstrate that aqueous extract of T. Laurifolia exerts hepatoprotective effect against alcoholic liver injury through a mechanism involving inhibition of oxidative stress and inflammation.

Effect of aqueous leaf extract of Thunbergia laurifolia on alcohol-induced liver injury in rats

Purpose: To investigate the antioxidant and anti-inflammatory effects of aqueous leaf extract of T. laurifolia against alcoholic liver injury in rats.&#x0D; Methods: Male Wistar rats were administered either normal saline, ethanol (EtOH), normal saline with low or high dose T. laurifolia leaf extract (TL-LD or TL-HD), EtOH with TL-LD or EtOH with TL-HD. Blood biochemical indices: hepatic malondialdehyde (MDA) levels, liver histopathology, hepatic cytochrome P450 2E1 (CYP2E1), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and pro-inflammatory cytokines, including interleukin 1 beta (IL-1β) and tumor necrotic factor alpha (TNF-α) mRNA expressions, were determined using standard methods.&#x0D; Results: The leaf extract of T. Laurifolia decreased hepatic MDA levels, improved liver pathology and down-regulated mRNA expressions of CYP2E1, NADPH oxidase and pro-inflammatory cytokinesin ethanol-treated rats.&#x0D; Conclusion: These results demonstrate that aqueous extract of T. Laurifolia exerts hepatoprotective effect against alcoholic liver injury through a mechanism involving inhibition of oxidative stress and inflammation.

Wild radish (Raphanus sativus var. hortensis f. raphanistroides) root extract protects neuronal cells by inhibiting microglial activation

External stimulus-induced activation of microglia plays an important role in the protection of neurons in the central nervous system; however, over-activation of microglia could cause neuronal damage, and it is implicated in the pathogenesis of neurodegenerative diseases. The aim of the present study was to investigate the effects of wild radish (Raphanus sativus var. hortensis f. raphanistroides) root extract (WRE) on microglial over-activation. Mouse microglia BV-2 cells and rat primary microglia were stimulated with lipopolysaccharide (LPS), treated with WRE, and analyzed for nitric oxide (NO) production, pro-inflammatory cytokine secretion, inducible NO synthase (iNOS) expression, and p38 kinase phosphorylation. Human neuroblastoma SH-SY5Y cells were treated with microglia-conditioned medium and analyzed for cell viability. Stimulation with LPS increased NO production and iNOS expression in BV-2 cells and primary microglia, but the treatment with WRE decreased both. Furthermore, WRE downregulated the mRNA expression and secretion of inflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), and inhibited the phosphorylation of p38 in LPS-activated microglia. Treatment with the conditioned medium of LPS-induced BV-2 cells decreased the viability of SH-SY5Y cells, but the damaging effect was significantly alleviated in cells treated with the conditioned medium of LPS plus WRE-cultured microglia. This indicated that the WRE treatment of microglia could protect neuronal cells from microglial activation-induced neurotoxicity. WRE may be a potential food product to attenuate neuroinflammation via the inhibition of microglial over-activation, which can slow down the neurodegenerative processes in the brain.

Effect of prostaglandin J_2 nanoparticles on repairing exercise-induced bone defect

The objective of this study was to investigate the effect of prostaglandin J_2 (PGJ_2) nanoparticles loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) for 15 days on repairing exercise-induced bone defects. Protein imprinting and real-time quantitative polymerase chain reaction were used to detect the effects of 15-deoxy-Δ12,14-PGJ_2 (15d-PGJ_2) nanoparticles on inflammatory factors in exercise-induced bone defects in rats. The osteogenic differentiation of rhBMP-2–PGJ_2 nanoparticles was detected by alkaline phosphatase staining and alkaline phosphatase content and osteocalcin content determination. The results show that 15d-PGJ_2 could inhibit the protein and gene expression of interleukin 6, interleukin 1 beta and tumor necrosis factor alpha in the tissues surrounding exercise-induced bone defects and upregulate the gene expression of bone morphogenetic protein 6 and platelet-derived growth factor subunit B, and that rhBMP-2–PGJ_2 nanoparticles could promote alkaline phosphatase staining, alkaline phosphatase activity and osteocalcin content. The following are the conclusions: 15d-PGJ_2 nanoparticles can inhibit the inflammatory reaction and increase the osteogenic activity in the exercise-induced bone defect area, rhBMP-2–PGJ_2 nanoparticles have a good effect on promoting the osteogenic differentiation of cells and both of them have a certain repair effect on the exercise-induced bone defect.

A STUDY ON PERFORMANCE EVALUATION OF SELECTED MUTUAL FUNDS IN INDIA

In the Indian Capital market various platforms for the investor to take a position their money for getting more return. Among equity share, bond, Treasury bill, bond, open-end fund then many, but within the Indian capital market, an open-end fund is one among the foremost favorable platforms for an investor to increase their wealth. That is why here we are conducting a study on selected mutual funds in India, the sample of the study is 7 mutual funds The Financial ratio analysis is employed for performance evaluation of fund, therein taking NAV (Net assets value) and return of the three years from 17th July 2017 to 2019. Finding Sharpe ratio, Variance, BETA, and Jenson's alpha on the bases of three-year data. In this study found market sentiment affect more in aggressive hybrid open-end fund compare to conservative.

Two new acylated triterpenoidal saponins from Gleditsia caspica Desf. and the effect of its saponin content on LPS-induced cognitive impairment in mice

• Two new triterpenoid saponins were isolated from Gleditsia caspica Desf. • Structures of saponins were determined using spectral and chemical means. • MEGC and SFGC were able to significantly improve memory and learning in mice dose dependently. Two bisdismosidic triterpenoidal saponins, caspicaoside A 1 (1) and caspicaoside B 1 (2) , were isolated from Gleditsia caspica fruit methanolic extract. The structures of 1 and 2 were determined using chemical and spectral techniques. Gleditsia caspica fruit methanolic extract (MEGC) and its saponin containing fraction (SFGC) at the two dose levels 45 and 90 mg/kg b.wt. were studied comparatively for their effect on LPS-induced cognitive impairment in mice using Ginkgo biloba (100 mg/kg b.wt.) as a standard drug. Neurobehavioral tests (Morris Water Maze and Novel Object Recognition tests) were conducted to prove that MEGC and SFGC at the two levels were able to significantly improve memory and learning in mice dose dependently. Also, the two test drugs were able to significantly decrease the levels of proinflammatory cytokines (Tumor necrosis factor alpha and Interleukin 1-beta) in addition to reducing the extra-cellular deposition of amyloid beta 42 in a dose dependent manner.