Immunohistochemical observations of the endocrine pancreas during metamorphosis of the sea lamprey,Petromyzon marinus L.

Summary Light-microscopic immunohistochemistry was used to localize insulin- and somatostatin-immunoreactive cells within developing endocrine pancreatic tissue of metamorphosing lampreys, Petromyzon marinus. The extrahepatic common bile duct and a portion of the intrahepatic bile duct develop into the caudal portion of the endocrine pancreas. The cranial pancreas is composed of follicles originating in the intestinal and diverticular epithelia, thus following the method of formation of pancreatic follicles from gut epithelium in larvae. In both the cranial and caudal portions, and in an intermediate cord of isolated follicles which connect these two major masses, insulin-immunoreactive cells appear first and are followed by cells showing somatostatin-immunoreactivity. In all stages of metamorphosis individual endocrine cells demonstrate immunoreactivity to a single hormone. Biliary atresia in lamprey may have some adaptive significance in providing cells that produce a caudal endocrine pancreas.Supported by NSERC of Canada grant No. A5945 and MRC of Canada grant No. MA8629 to JHY     

普济痔疮栓联合化浊解毒方保留灌肠治疗肛窦炎的疗效及对疼痛介质、免疫功能和复发率的影响

摘要 目的：探讨普济痔疮栓联合化浊解毒方保留灌肠治疗肛窦炎的疗效及对疼痛介质、免疫功能和复发率的影响。方法：选取我院2020年1月至2021年7月确诊的100例肛窦炎患者。按随机数字表法分为对照组（普济痔疮栓治疗,50例）和实验组（普济痔疮栓联合化浊解毒方保留灌肠治疗,50例）。对比两组疗效、中医证候积分、疼痛介质、免疫功能和复发率的变化情况。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组治疗2个疗程后肛门坠胀及隐痛、排便不尽感、肛门潮湿评分低于对照组（P<0.05）。实验组治疗2个疗程后CD8⁺低于对照组;CD3⁺、CD4⁺、CD4⁺/CD8⁺高于对照组（P<0.05）。实验组治疗2个疗程后前列腺素E2（PGE2）、P物质（SP）、多巴胺（DA）、五羟色胺（5-HT）低于对照组（P<0.05）。实验组治疗后4个月、6个月的复发率低于对照组（P<0.05）。结论：普济痔疮栓联合化浊解毒方保留灌肠治疗肛窦炎,可促进临床症状改善,降低复发率,可能与降低疼痛介质水平和调节机体免疫功能有关。     

Development and physiology of follicular atresia during ovarian growth in the house fly, Musca domestica

Atretic follicles regularly occur in the ovary of the house fly, Musca domestica. The frequency of ovarian follicular atresia and the proportion of atretic follicles per ovary are related to the stage of oögenesis and to the age of the females. Only vitellogenic follicles may become atretic. The atresia may occur at any stage of vitellogenesis, though most follicles become atretic in mid-vitellogenesis. Atretic follicles are completely resorbed within 24–36 hr. The follicle cells may play a synthesizing role during growth and disintegrating one during follicle resorption. The induction of glycogen synthesis by the cessation of RNA and protein synthesis and by vitellogenesis in normal follicles is discussed. The same processes occur prematurely in the atretic follicle which can be thus distinguished by a high content of glycogen.     

Editorial: Twin peaks mission

The Y human chromosome has many ancient genes whose fidelity seems to have been preserved by tandem sequences and palindromic ‘hairpins’, compared/repaired by ‘gene conversion’. That a primary function of recombination machinery is DNA repair has been suggested, and rejected, several times; this new evidence is very persuasive. The process, better called gene conservation than gene conversion, could operate in all diploid organisms, accounting for the retention of long gene sequences without ‘informational meltdown’ ('concerted evolution'). It resembles rocket‐science computer‐redundancy error‐checking, comparison of three or four sequences, not just two. If recognition of errors in ‘converted’ sequences can be followed by either repair or rejection, the rejection option can account for the vast wastage of meiotic products. The repair option might be used in Drosophila oocytes and even zygotic nuclei, possibly other oocytes, ancient asexual lineages such as mycorrhizal fungi, perhaps the Y itself. Both evolutionary stasis (conservatism) and development and deployment of complex developmental modules can be understood in these terms so both the evolution of biodiversity and the practice of systematics may have these mechanisms as their bases. The main individual‐fitness and evolutionary advantages of diploidy were not primarily cloaking of recessive al‐leles, or allelic recombination and Mendelism, but conserving long DNA sequences.     

MicroRNA-205 affects mouse granulosa cell apoptosis and estradiol synthesis by targeting CREB1

MicroRNA-205 (miR-205) is involved in various physiological and pathological processes, but its biological function in follicular atresia remains unclear. In this study, we investigated miR-205 expression in mouse granulosa cells (mGCs) and analyzed its functions in primary mGCs by performing a series of in vitro experiments. Quantitative real-time polymerase chain reaction showed that miR-205 expression was significantly higher in early atretic follicles and progressively atretic follicles than in healthy follicles. miR-205 overexpression in mGCs significantly promoted apoptosis and caspase-3/9 activities, as well as inhibited estrogen (E2) release and cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1, a key gene in E2 production) expression. Bioinformatics and luciferase reporter assays revealed that the gene encoding cyclic AMP response element (CRE)-binding protein 1 (CREB1) was a direct target of miR-205 in mGCs. CREB1 upregulation partially rescued the effects of miR-205 on apoptosis, caspase-3/9 activities, E2 production, and CYP19A1 expression on mGCs. These results indicate that miR-205 might play an important role in ovarian follicular development and provide new insights into follicular atresia     

Prognostic molecular markers in pediatric liver disease – Are there any?

Pediatric liver disease (PLD) is a major cause of severe morbidity and prolonged hospitalizations in children. Stratifying patients in terms of prognosis remains challenging. The limited knowledge about molecular mechanisms causing and accompanying PLD remains the main obstacle in a search for reliable prognostic biomarkers. A systematic search of MEDLINE via PubMed and Embase via OVID was conducted on studies published between August 2007 and August 2017. Molecular markers with a prognostic potential in terms of survival, need for liver transplantation or disease progression/regression were selected. In general, identified studies were single center smaller case-control studies or case series with a low level of evidence and a high risk of bias. Only 23 studies comprising 898 patients could be included, mostly focusing on biliary atresia, non-alcoholic fatty liver disease, viral hepatitis, and LT; and markers related to morphogenesis and fibrosis. Furthermore, molecular markers in metabolic pathways and inflammation shown to be relevant, however requiring further validation. Hence, further biological and clinical studies are needed to gain greater molecular insight into PLD.     

Yolk proteolysis in rainbow trout oocytes after serum-free culture: evidence for a novel biochemical mechanism of atresia in oviparous vertebrates

Our recent studies show little evidence for increased granulosa cell apoptosis during atresia in teleost follicles, in direct contrast to the mammalian model. Histological evidence suggests that atresia in many oviparous vertebrates involves proteolytic degradation of the energy-rich yolk storage proteins within the oocyte. This study tests the hypothesis that physiological conditions that promote atresia (hormone withdrawal) lead to increased lysosomal protease activity in rainbow trout oocytes. We subjected rainbow trout ovarian follicles to conditions that promote atresia (serum-free culture) for up to 72 hr, and measured the activity of lysosomal proteases using routine enzymatic assays. Furthermore, we used high performance liquid chromatography to quantify the increase in free amino acids resulting from proteolysis of yolk proteins. Concomitantly, we evaluated the extent of follicular apoptosis during prolonged serum-free culture, using caspase-3-like activity and DNA fragmentation as indicators of apoptosis. Our results show a significant, time-dependent increase in cathepsin L-like, but not cathepsin D-like, activity levels during culture in serum-free medium; increased cathepsin L-like activity is confirmed by a significant increase in oocyte free amino acid content after 72 hr culture. In contrast, we detected only a transient increase in apoptosis during prolonged serum-free culture, as revealed through both radioactive 3'end-labeling of oligonucleosomal DNA fragments, and caspase-3-like activity. The results of this study provide the first evidence for a novel mechanism of follicular atresia in teleosts involving cathepsin-mediated yolk proteolysis.     

Exposure Duration‐Dependent Ovarian Recovery in Methoxychlor‐Treated Mice

The pesticide methoxychlor (MXC) is known to target ovarian antral follicles in the mouse. In previous in vivo studies, MXC administration for 20 days increased atresia, but did not affect female fertility immediately after dosing. Thus, we hypothesized that perhaps not enough time had elapsed between the onset of MXC‐induced atresia and actual follicle loss to result in reduced fertility. The current study was undertaken to determine whether MXC treatment for 20 days results in reduced antral follicle numbers and fertility at 30 and 60 days after dosing. To test this hypothesis, adult CD‐1 female mice were dosed with vehicle control or MXC (64 mg/kg/day) for 20 days. At 30 and 60 days postdosing, the mice were either subjected to fertility tests or their ovaries were collected and subjected to histological evaluation of follicle numbers and atresia. The results indicate that at 30 days after the completion of dosing, MXC significantly increased atresia and reduced primordial and total follicle numbers, but did not affect fertility compared to controls. At 60 days after completion of dosing, MXC did not significantly affect fertility, follicle numbers, or atresia compared to controls. Collectively, these data indicate that the ovary may be able to recover from MXC treatment for 20 days