Amylase intrapancreatic infusion delays insulin release during an intravenous glucose tolerance test,proof of acini–islet–acinar interactions

BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ.METHODS The study was performed on six pigs under general anesthesia.An intravenous glucose tolerance test was performed,with a bolus infusion of 50%glucose to the jugular vein,while amylase(5000 U/kg)or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate.RESULTS The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion,for>1 h.The intrapancreatic infusion of the vehicle(saline)did not have any effect on the time frame of insulin release.Infusion of 1%bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion,far beyond the glucose peak.CONCLUSION Intrapancreatic arterial infusion of amylase interrupted the integrated glucose–insulin interactions.This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.

Modulators of alternative splicing as novel therapeutics in cancer

Alternative splicing(AS), the process of removing introns from pre-m RNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several dise-ases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.

3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease

Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and IVDD.Deep learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.

Effect of Cymbopogon citratus Stapf extract on lipid profile and antioxidant status in streptozotocin-induced diabetic rats

OBJECTIVE To investigate the effects of Cymbopogon citratus Stapf water extract on lipid profile and antioxidant status in streptozotocin-induced diabetic rats.METHODS Diabetes was induced by injection of streptozotocin(STZ,50mg·kg-1)intraperitoneally.Diabetic rats were divided into 5groups,consisting of 6rats.GroupⅠ,reserved as diabetic control,was administered distilled water and groupⅡ,reserved as positive control,was administered glibenclamide(10mg·kg-1·d-1)throughout the duration of the experiment.Those in groupⅢ,ⅣandⅤ were administered 250,500 and 1000mg·kg-1·d-1 of the extract,respectively for 28 d.RESULTS Treatment with 500 and 1000mg·kg-1·d-1 of the extract resulted in reduction of serum AST,ALT,serum cholesterol,triglycerides and LDL,whereas HDL was found to be increased compared with diabetic control rats(P<0.05).Moreover,increased serum activities of superoxide dismutases and catalase were found in diabetic rats treated with the extract whereas serum thiobarbituric acid reactive substance was decreased,in comparison with diabetic control rat(P<0.05).CONCLUSION Cymbopogon citratus Stapf water extract provides a benefit effect on serum lipid and antioxidant effect in diabetic rats.Thus,the extract may lower cardiovascular disease risk and others complications related to hyperlipidemia and oxidative stress in diabetic patients.

脑干背侧迷走神经复合体中星形胶质细胞对食物摄取的调节

随着下丘中与调节能量稳态有关的脑星形胶质细胞信号传导的发现,星形胶质细胞在控制摄食的脑回路中的作用正逐渐被认识。脑干背侧迷走神经复合体(DVC)内的孤束核(NTS)整合了来自内脏的迷走神经传入信息,并起调节摄食的作用。我们假定该核团中的星形胶质细胞对食物摄入做出反应并影响食物摄入。在黑暗期喂食高脂食物12 h的小鼠出现NTS星形胶质细胞活化,表现为与对照饲料喂养的小鼠相比,极后区(AP)邻近的神经胶质纤维酸性蛋白(GFAP)免疫反应性细胞数量增加(65%)和形态复杂性增高。为了检测星形胶质细胞活化对食物摄入的影响,我们使用腺相关病毒(AAV)载体(AAV-GFAPh M3Dq-m Cherry)将设计药物激活的设计受体(DREADDs)导入DVC星形胶质细胞(包括孤束核、极后区和迷走神经背运动核)。使用氯氮平-N-氧化物(0.3 mg/kg)进行化学遗传激活星形胶质细胞使其产生了比平行处理组星形细胞更复杂的形态,并在注射后4 h使动物在黑暗期进食减少84%。与表达AAV-GFAPm Cherry的对照小鼠相比,DVC星形胶质细胞的h M3Dq激活在禁食过夜后仍然减少黑暗期摄食(注射后4 h降低71%)。DREADD介导的星形胶质细胞激活不影响运动功能。DVC中星形胶质细胞的h M3Dq激活引起邻近的摄食神经回路(包括臂旁核)中c-FOS的表达。这表明NTS星形胶质细胞能对急性营养过剩做出反应,参与外周饱腹感信号的整合,并且在其激活后可以减少食物摄入。

Osteomodulin downregulation is associated with osteoarthritis development

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis(OA), and osteomodulin(OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.

Ad libitum water consumption prevents exercise-associated hyponatremia and protects against dehydration in soldiers performing a 40-km route-march

Background: It remains unclear if ad libitum water drinking, as a hydration strategy, prevents exercise-associated hyponatremia(EAH) during prolonged exercise. The aim of this study was to determine the incidence of EAH within the broader context of fluid regulation among soldiers performing a 40-km route-march ingesting water ad libitum.Methods: Twenty-eight healthy male soldiers participated in this observational trial. Pre-and post-exercise body mass, blood and urine samples were collected. Blood samples were assessed for serum sodium([Na+]), glucose, creatinine, urea nitrogen(BUN), plasma osmolality, creatine kinase(CK), and plasma arginine vasopressin(AVP) concentrations. Plasma volume(PV) was calculated using hematocrit and hemoglobin. Urine samples were analyzed for osmolality and (Na+)Water intake was assessed by weighing bottles before, during and after the march. The mean relative humidity was 55.7%(21.9–94.3%) and the mean dry bulb temperature was 27.1°C(19.5°C-37.0°C) during the exercise.Results: Twenty-five soldiers(72±10 kg)(Mean±SD) completed the march in 09:11±00:43(hr:min). Participants consumed 736±259 ml/h of water and lost 2.8±0.9 kg(4.0%±1.4%, P<0.05) of body mass. Significant(pre-march vs. post-march;P<0.05) decreases in serum [Na+](141 mmol/L vs. 136 mmol/L), plasma osmolality(303 m Osmol/kg H2O vs. 298 m Osmol/kg H2O), and serum creatinine(111 μmol/L vs. 101 μmol/L) and urine [Na+](168 mmol/L vs. 142 mmol/L), as well as significant increases in plasma AVP(2 pg/ml vs. 11 pg/ml), plasma CK(1423 U/L vs. 3894 U/L) and urine osmolality(1035 m Osmol/kg H2O vs. 1097 m Osmol/kg H2O) were found. The soldier(72 kg) with the lowest postexercise sodium level completed the march in 08:38. He drank 800 ml/h, lost 2% body mass, and demonstrated(prepost) increases in plasma osmolality(294–314 m Osmol/kg H2O), BUN(20–30 mg/dl), AVP(2–16 pg/ml) and PV(41%). His urine osmolality decreased from 1114 m Osmol/kg H2O to 1110 m Osmol/kg H2O. No participants finished the route-march with a serum [Na+] indicating hypernatremia(range, 134–143 mmol/L).Conclusions: Ad libitum drinking resulted in 4% body mass loss with a 2 mmol/L serum [Na+] reduction in conjunction with high urine osmolality(>1000 m Osmol/kg H2O) and plasma AVP. No single hydration strategy likely prevents EAH, but hypernatremia(cellular dehydration) was not seen despite >2% body mass losses and high urine osmolality.

Stable isotope analysis of diet confirms niche separation of two sympatric species of Namib Desert lizard

We used stable isotopes of carbon and nitrogen to study the trophic niche of two species of insectivorous lizards,the Husab sand lizard Pedioplanis husabensis and Bradfield’s Namib day gecko living sympatrically in the Namib Desert.We measured theδ13C andδ15N ratios in lizard blood tissues with different turnover times(whole blood,red blood cells and plasma)to investigate lizard diet in different seasons.We also measured theδ13C andδ15N ratios in available arthropod prey and plant tissues on the site,to identify the avenues of nutrient movement between lizards and their prey.Through the use of stable isotope mixing models,we found that the two lizard species relied on a largely non-overlapping but seasonally variable array of arthropods:P.husabensis primarily fed on termites,beetles and wasps,while R.bradfieldi fed mainly on ants,wasps and hemipterans.Nutrients originating from C3 plants were proportionally higher for R.bradfieldi than for P.husabensis during autumn and late autumn/early winter,although not summer.Contrary to the few available data estimating the trophic transfer of nutrients in ectotherms in mixed C3 and C4/crassulacean acid metabolism(CAM)plant landscapes,we found that our lizard species primarily acquired nutrients that originated from C4/CAM plants.This work adds an important dimension to the general lack of studies using stable isotope analyses to estimate lizard niche partitioning and resource use.

Design and performance evaluation of additively manufactured composite lattice structures of commercially pure Ti(CP-Ti)

Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural,mechanical,and biological properties.In this study,six types of composite lattice structures with different strut radius that consist of simple cubic(structure A),body-centered cubic(structure B),and edge-centered cubic(structure C)unit cells are designed.The designed structures are firstly simulated and analysed by the finite element(FE)method.Commercially pure Ti(CP-Ti)lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting(SLM),and the dimensions,microtopography,and mechanical properties are characterised.The results show that among the six types of composite lattice structures,combined BA,CA,and CB structures exhibit smaller maximum von-Mises stress,indicating that these structures have higher strength.Based on the fitting curves of stress/specific surface area versus strut radius,the optimized strut radius of BA,CA,and CB structures is 0.28,0.23,and 0.30 mm respectively.Their corresponding compressive yield strength and compressive modulus are 42.28,30.11,and 176.96 MPa,and 4.13,2.16,and 7.84 GPa,respectively.The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone,which makes it a potential candidate for subchondral bone restorations.

Body temperature,activity patterns and hunting in free-living cheetah:biologging reveals new insights

As one of the few felids that is predominantly diurnal,cheetahs(Acinonyx jubatus)can be exposed to high heat loads in their natural habitat.Little is known about long-term patterns of body temperature and activity(including hunting)in cheetahs because long-term concurrent measurements of body temperature and activity have never been reported for cheetahs,or,indeed,for any free-living felid.We report here body temperature and locomo-tor activity measured with implanted data loggers over 7 months in 5 free-living cheetahs in Namibia.Air tem-perature ranged from a maximum of 39°C in summer to−2°C in winter.Cheetahs had higher(~0.4°C)max-imum 24-h body temperatures,later acrophase(~1 h),with larger fluctuations in the range of the 24-h body temperature rhythm(approximately 0.4°C)during a hot-dry period than during a cool-dry period,but main-tained homeothermy irrespective of the climatic conditions.As ambient temperatures increased,the cheetahs shifted from a diurnal to a crepuscular activity pattern,with reduced activity between 900 and 1500 hours and increased nocturnal activity.The timing of hunts followed the general pattern of activity;the cheetahs hunted when they were on the move.Cheetahs hunted if an opportunity presented itself;on occasion they hunted in the midday heat or in total darkness(new moon).Biologging revealed insights into cheetah biology that are not ac-cessible by traditional observer-based techniques.

利益冲突与婴儿配方奶粉行业:行动呼吁

母乳喂养是改善儿童健康和生存最具有成本效益的干预措施之一,对于家庭和社会而言,都有着重要的近期和远期利益、然而,实力强大的跨国配方奶粉制造商竞争婴儿喂养市场份额的行为,破坏了支持母乳喂养的政策和干预措施的制定与实施。