Loss of diurnal behavioral rhythms and impaired lipid metabolism in growing pigs with mistimed feeding.

The misalignment of eating time and the endogenous circadian rhythm impairs the body's ability to maintain homeostasis. Although it is well established that children and growing animals differ from adults in their energy metabolism and behavioral patterns, little is known about how mistimed feeding disturbs the diurnal rhythms of behavior and metabolism in children and growing diurnal animals. In this study, growing pigs (diurnal animal) were randomly assigned to the daytime-restricted feeding (DRF) and nighttime-restricted feeding (NRF) groups for 5 weeks. Compared with observations in the DRF group, NRF disrupted the diurnal rhythm of behavior and clock genes and lowered the serum ghrelin, dopamine, and serotonin levels during the daytime and nighttime. Microbiome analysis results suggested that NRF altered the diurnal rhythm and composition of the gut microbiota, and increased log-ratios of Catenibacterium:Butyrivibrio and Streptococcus:Butyrivibrio. Based on the serum proteome, the results further revealed that rhythmic and upregulated proteins in NRF were mainly involved in oxidative stress, lipid metabolism, immunity, and cancer biological pathways. Serum physiological indicators further confirmed that NRF decreased the concentration of melatonin and fibroblast growth factor 21 during the daytime and nighttime, increased the diurnal amplitude and concentrations of very-low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increased the apolipoprotein B/ApoA1 ratio, which is a marker of metabolic syndrome. Taken together, this study is the first to reveal that mistimed feeding disrupts the behavioral rhythms of growing pigs, reprograms gut microbiota composition, reduces the serum levels of hormones associated with fighting depression and anxiety, and increases the risk of lipid metabolic dysregulation.

Night-restricted feeding improves locomotor activity rhythm and modulates nutrient utilization to accelerate growth in rabbits.

An unfavorable lifestyle disrupts the circadian rhythm, leading to metabolic dysfunction in adult humans and animals. Increasing evidence suggests that night-restricted feeding (NRF) can effectively prevent ectopic fat deposition caused by circadian rhythm disruption, and reduce the risk of metabolic diseases. However, previous studies have mainly focused on the prevention of obesity in adults by regulating dietary patterns, whereas limited attention has been paid to the effect of NRF on metabolism during growth and development. Here, we used weaning rabbits as models and found that NRF increased body weight gain without increasing feed intake, and promoted insulin-mediated protein synthesis through the mTOR/S6K pathway and muscle formation by upregulating MYOG. NRF improved the circadian clock, promoted PDH-regulated glycolysis and CPT1B-regulated fatty-acid ß-oxidation, and reduced fat content in the serum and muscles. In addition, NRF-induced body temperature oscillation might be partly responsible for the improvement in the circadian clock and insulin sensitivity. Time-restricted feeding could be used as a nondrug intervention to prevent obesity and accelerate growth in adolescents.

Effect of precision air supply cooling system with different cooling air speed on reproductive performance, stress status, immunoglobulin and fecal microbiota of lactating sows.

This study investigated the precision air supply cooling system with different cooling air speed on reproductive performance, stress status, immunity and intestinal microbiota of sows. A total of 36 sows were randomly assigned into three groups: control group (CON, n = 12) without cooling system, low cooling air speed (2.24 ± 0.11 m/s) group (LCAS, n = 12) with precision air supply cooling system, high cooling air speed (3.33 ± 0.11 m/s) group (HCAS, n = 12) with precision air supply cooling system. The average daily ambient temperature and relative humidity in experimental farrowing rooms were 28 °C-32 °C and 65%-90%, respectively, during daytime (8:00-20:00). The reproductive performance, respiratory rate (RR), body surface temperature (BST), rectal temperature (RT) salivary parameters and fecal microbiota of lactating sows were measured. The results showed that compared with CON group, average daily feed intake of sows and average daily gain of piglets were increased (P < 0.05) in LCAS and HCAS groups. The RR, BST and RT were decreased (P < 0.05) in LCAS and HCAS groups in wk 1 before parturition and wk 2 after parturition. The salivary cortisol and alpha amylase level of LCAS and HCAS sows were decreased (P < 0.05) on d 14 after parturition, while the salivary immunoglobulin A and immunoglobulin G level of LCAS and HCAS sows were increased (P < 0.05) on d 7 after parturition. The LCAS and HCAS sows showed higher relative abundance of Clostridium_sensu_stricto_1 in feces, which was positively associated with immunoglobulin A (P < 0.01). In conclusion, both low and high cooling air speed improved reproductive performance, alleviated stress status, and enhanced salivary immunoglobulins and beneficial fecal microbiota community in lactating sows, which indicated that precision air supply cooling system could be an effective cooling strategy for lactating sows in high ambient temperature.

Early Forebrain Neurons and Scaffold Fibers in Human Embryos.

Neural progenitor proliferation, neuronal migration, areal organization, and pioneer axon wiring are critical events during early forebrain development, yet remain incompletely understood, especially in human. Here, we studied forebrain development in human embryos aged 5 to 8 postconceptional weeks (WPC5-8), stages that correspond to the neuroepithelium/early marginal zone (WPC5), telencephalic preplate (WPC6 & 7), and incipient cortical plate (WPC8). We show that early telencephalic neurons are formed at the neuroepithelial stage; the most precocious ones originate from local telencephalic neuroepithelium and possibly from the olfactory placode. At the preplate stage, forebrain organization is quite similar in human and mouse in terms of areal organization and of differentiation of Cajal-Retzius cells, pioneer neurons, and axons. Like in mice, axons from pioneer neurons in prethalamus, ventral telencephalon, and cortical preplate cross the diencephalon-telencephalon junction and the pallial-subpallial boundary, forming scaffolds that could guide thalamic and cortical axons at later stages. In accord with this model, at the early cortical plate stage, corticofugal axons run in ventral telencephalon in close contact with scaffold neurons, which express CELSR3 and FZD3, two molecules that regulates formation of similar scaffolds in mice.

Assessing impact of risk perception and environmental regulation on household carcass waste recycling behaviour in China.

Carcass waste recycling exerts an important influence on preventing epidemic diseases, improving the ecological environment, and promoting sustainable development of the livestock industry although it has rarely aroused widespread attention throughout the world. Based on the data of 470 households engaged in breeding pigs in Hebei, Henan, and Hubei, China, and considering dead pigs as an example, this study employed the Double Hurdle model to assess impact of risk perception on household dead pig recycling behaviour and further tested the moderating effects of environmental regulation on the impact of risk perception on household dead pig recycling behaviour. The results show that: (1) Risk perception has a positive and significant influence on household dead pig recycling behaviour; however, this influence is mainly caused by households' production and public health safety risk perceptions. Food and ecological safety risk perceptions have no significant influence on household dead pig recycling behaviour. (2) Environmental regulation has enhanced moderating effects on the impact of risk perception on household dead pig recycling behaviour, but the moderating effects mainly arose from imperative, guiding, and voluntary regulations. A moderating effect of incentive regulation is not obvious. (3) The moderating effects of environmental regulations present strong heterogeneity when different breeding scales and recycling technical attributes are considered. Finally, some policy implications, such as improving households' risk perception level, enhancing environmental regulation intensity, and classifying to formulate measures, are proposed.

Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.

Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon-telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.

A role for atypical cadherin Celsr3 in hippocampal maturation and connectivity.

Atypical cadherin Celsr3, a regulator of planar cell polarity, is critical for the development of the axonal blueprint. We previously showed that expression of Celsr3 is necessary to establish forebrain connections such as the anterior commissure and thalamocortical and corticospinal tracts. The requirement for Celsr3 during hippocampal wiring and its action in the hippocampus remain largely unexplored. Here, we compared the connectivity and maturation of the hippocampal formation in Celsr3|Foxg1 and Celsr3|Dlx mice. Celsr3 is inactivated in the whole telencephalon, including the hippocampal primordium, in Celsr3|Foxg1 mice, and in the early basal telencephalon, including ganglionic eminences and ventral diencephalon, in Celsr3|Dlx mice. Behavioral tests showed that both mutants were hyperactive and had impaired learning and memory. Abnormal cytoarchitecture of CA1, CA3, and dentate gyrus was found in the Celsr3|Foxg1 mutant, in which afferent and efferent hippocampal pathways, as well as intrinsic connections, were dramatically disrupted. In Celsr3|Dlx mutant mice, hippocampal cytoarchitecture was mildly affected and extrinsic and intrinsic connectivity moderately disturbed. In both mutants, pyramidal neurons in CA1 harbored atrophic dendritic trees, with decreased synapse density and increased proportion of symmetric versus asymmetric synapses, and long-term potentiation was altered. In contrast, mutant hippocampal neurons extended neurites that were normal, even longer than those of control neurons, indicating that anomalies in vivo are secondary to defective connections. Postnatal neurogenesis was preserved and mutant interneurons were able to migrate to the hippocampus. Thus, like in neocortex, Celsr3 is required for hippocampal development, connectivity and function, and for pyramidal cell maturation.

An Evaluation of the Crop Preference and Phenotypic Characteristics of Ceracris kiangsu Tsai (Orthoptera: Arcypteridae) under Different Temperatures.

The yellow-spined bamboo locust (YSBL), Ceracris kiangsu Tsai, has historically had a significant impact on different bamboo varieties in East Asia and Southeast Asia. Since 2014, there have been many outbreaks of YSBL populations in Laos, and YSBLs subsequently invaded Southwest China in 2020 and 2023. However, there was limited information about the damage to staple crops. Life table parameters and fitness parameters were assessed using wheat, rice, waxy maize, and sweet maize under three different temperatures (25 °C, 30 °C, and 35 °C) in the laboratory. The results indicated that the YSBLs feeding on wheat seedlings displayed a significantly higher survival rate, a shorter developmental time, and a higher adult emergence rate compared to YSBLs feeding on the other host species at 30 °C. The developmental durations of 1st and 3rd instar YSBLs on wheat (1st: 8.21 ± 0.35 d; 3rd: 6.32 ± 0.34 d) and rice (1st: 7.19 ± 0.23 d; 3rd: 9.00 ± 0.66 d) were significantly shorter than those of 1st and 3rd instar YSBLs on waxy maize (1st: 13.62 ± 1.22 d; 3rd: 13.67 ± 6.33 d) and sweet maize (1st: 16.00 ± 1.79 d; 3rd: 18.00 ± 3.49 d) at 30 °C. The body lengths of male and female YSBLs on wheat (male: 29.52 ± 0.40 mm, female: 34.97 ± 0.45 mm) and rice (male: 28.85 ± 0.68 mm, female: 34.66 ± 0.35 mm) were significantly longer than those observed when they were fed on sweet maize (male: 25.64 ± 1.60 mm, female: 21.93 ± 6.89 mm). There were only male adults obtained on waxy maize. The phenotypic characteristics of the YSBLs feeding on rice seedlings were very close to those of the YSBLs feeding on wheat seedlings. A relatively slower decline was observed in the survival rates of YSBL nymphs on wheat and rice compared to those on waxy maize and sweet maize at 25 °C, 30 °C, and 35 °C. In short, this study implied that YSBLs prefer wheat and rice. This study is the first report of direct damage caused by the YSBL to wheat in the laboratory, and its results could be useful in improving our understanding of the host preference of the YSBL and providing strategies for the management of this pest in field crops.

Reproduction system development of Ceracris kiangsu Tsai female adults and its relationship with fitness characteristics.

Research on the ovarian development of insect pests helps provide key information for predicting pest occurrences, and currently, there is very limited information about the reproductive system of Ceracris kiangsu Tsai. This study aimed to assess the reproductive fitness of 321 adult female insects by using traditional methods to dissect female adults, measure female ovaries, and assess the process of egg formation. The phenotypic traits including body weight and body length were also measured and used to estimate the model of ovarian developmental stages. Four ovarian developmental stages before the oviposition were identified, and the fundamental ovarian structure of C. kiangsu displayed red dots on the matured eggs inside the calyx at ovarian developmental stage V. The accessory glands of C. kiangsu had the deepest folds at stage Ⅲ. Redundancy analysis (RDA) was used to explore the correlation between ovarian development, body weight, and body length. A significant positive correlation was observed for body weight (p = 0.001) and body length (p = 0.009), which varied with the grade of ovarian development evaluated by the ovarian developmental stage, ovarian length, ovarian width, and ovarian cross-sectional area. A partial least square (PLS) regression was used to model the ovarian developmental stage, with a stage-based PLS being identified as the more effective method, which was y = 1.509x 1 + 0.114x 2. The model provides a potentially rapid way to identify the population source as either "native" or "immigrant" from the phenotypic traits without dissection. The aforementioned model may be used to estimate adult emergence periods and identify migratory populations from their ovarian development, potentially aiding in implementing proper prevention measures.

Daily activity patterns and body temperature of the Oriental migratory locust, Locusta migratoria manilensis (Meyen), in natural habitat.

Current pest management techniques would benefit from understanding the behavioural rhythms of the target pest and its body temperature, a critical aspect not well studied and potentially limiting the effectiveness of biopesticides under natural conditions. This study aims 1) to understand under natural conditions the behavioural patterns of different stages of hoppers and adults of Locusta migratoria manilensis and 2) to identify the environmental factors modulating their body temperature through field observation. We carried out an intensive field sampling in two of the main locust breeding regions in China, recording the body temperature (day and night), morphological traits (stage, sex and size) and microhabitat of 953 individuals. The results revealed that locusts preferred the ground as their main activity subhabitat, particularly for hoppers. Adults tended to move upper in the reed canopy at two peaks (10-11 h and 14-15 h). Locusts body temperature during daytime increased with development stage and size, while the opposite pattern occurred during night time. Entompathogenic fungi are more effective if the body temperature of the target pest is in a proper range without too high or too low. Application of biopesticides should focus on younger locusts spraying in the morning or at dusk as the locusts have lower body temperatures.

Celsr2 Knockout Alleviates Inhibitory Synaptic Stripping and Benefits Motoneuron Survival and Axon Regeneration After Branchial Plexus Avulsion.

Axotomy-induced synaptic stripping modulates survival and axon regeneration of injured motoneurons. Celsr2 is supposed to mediate homophilic interactions of neighboring cells during development, and its role in synaptic stripping remains unknow. In a model of brachial plexus avulsion, Celsr2 knockout improved functional recovery, motoneuron survival, and axon regeneration. Celsr2 was indicated to express in spinal motoneurons, excitatory and inhibitory interneurons, astrocytes, and a subset of oligodendrocytes using Celsr2LacZ mice. Double immunostaining showed that the coverage of inhibitory and excitatory vesicles on injured motoneurons were remarkably reduced after injury, whereas more inhibitory vesicles were maintained in Celsr2-/- mutants than control mice. In the ultrastructure, the density of inhibitory F-boutons on injured motoneurons was higher in Celsr2-/- mutants than controls. Conditional knockout of Celsr2 in astrocytes or oligodendrocytes showed the similar axotomy-induced synaptic withdrawal to the control. RNAseq of injured spinal samples identified 12 MHC I molecules with significant changes between Celsr2-/- and control mice. After injury, expression of MHC I surrounding injured motoneurons was increased, particularly high in Celsr2-/- mutants. In conclusion, Celsr2 knockout enhances MHC I signaling, alleviates inhibitory synaptic stripping cell-autonomously, and contributes to motoneuron survival and regeneration, and Celsr2 is a potential target for neural repair.

Dual targeting, a new strategy for novel PARP inhibitor discovery.

As a hallmark for cancer treatment, PARP inhibitors can effectively kill tumor cells with a mechanism termed as synthetic lethality, and are used to treat various cancers including ovarian, breast, prostate, pancreatic and others with DNA repair defects. However, along with the clinical trials progressing, the limitations of PARP-1 inhibitors became apparent such as limited activity and indications. Studies have shown that a molecule that is able to simultaneously restrict two or more targets involving in tumors is more effective in preventing and treating cancers due to the enhancing synergies. In order to make up for the shortcomings of PARP inhibitors, reduce the development cost and overcome the pharmacokinetic defects, multiple works were carried out to construct dual targeting PARP inhibitors for cancer therapy. Herein, they were summarized briefly.

Effect of Different Cross-Fostering Strategies on Growth Performance, Stress Status and Immunoglobulin of Piglets.

The effect of different cross-fostering strategies on the growth performance, stress and immunity of piglets was investigated in this study. In the first experiment, a total of 20 litters (i.e., 20 sows) and 120 piglets were classified into one of six treatments in a 2 × 3 factorial arrangement. The treatments consisted of piglets without or with cross-fostering and different birth weights (low birth weight, LBW; intermediate birth weight, IBW; high birth weight, HBW). The weaning weight (WW) and average daily gain (ADG) of LBW piglets and IBW piglets were not significantly different between the not cross-fostered (NC-F) group and the cross-fostered (C-F) group. There was a higher (p < 0.05) ADG in the control piglets compared with the cross-fostered piglets. This effect on ADG was only seen in the HBW piglets. In the second experiment, six sows with a similar body condition and farrowed on the same day were selected. Three female piglets with a birth weight of 0.6-0.85 kg were selected from each litter as experimental piglets. Eighteen piglets were grouped into three treatments: (1) not cross-fostered (NC-F1), (2) cross-fostered at 36-48 h after birth (C-F1), (3) cross-fostered at day 7 after birth (C-F2). The growth performance of NC-F1 and C-F1 piglets was higher than C-F2 piglets (p < 0.05), and the suckling positions of NC-F1 and C-F1 piglets on days 8, 12, 16 and 20 were more forward than the C-F2 piglets (p < 0.05). Plasma cortisol (COR) concentrations of NC-F1 and C-F1 piglets were lower than C-F2 piglets (p < 0.05). A significant negative correlation was observed between BW at day 21 and plasma COR concentration. In conclusion, cross-fostering within 24 h of birth has adverse influences on the ADG of HBW piglets, while it has no negative effect on the ADG of LBW and IBW piglets. Moreover, for IBW piglets, late cross-fostering (i.e., on day 7 after farrowing) has negative impacts on the growth performance and teat order of piglets, and it increases the cortisol level of piglets.

Prolonged melatonin treatment promote testicular recovery by enhancing RAC1-mediated apoptotic cell clearance and cell junction-dependent spermatogensis after heat stress.

INTRODUCTION: A decline in semen quality caused by global warming and torrid working conditions is a major cause of human male infertility, and heat stress-induced decreases in male reproductive ability results in economic losses in livestock husbandry. Increasing evidence suggests that melatonin exerts protective effects on stress-induced DNA damage and apoptosis in germ cells. However, few studies have assessed the effects of melatonin on testicular recovery during post-heat stress and the underlying mechanisms. METHODS AND RESULTS: In vivo studies using 8-week-old male CD-1 mice revealed that melatonin pretreatment (50 mg/kg for 5 days) did not alleviate heat stress-induced germ cell loss and disrupted testicular histomorphology, however, long-term melatonin administration after heat stress accelerated germ cell apoptosis, spermatogenic cell regeneration, and testicular weight recovery. In vitro studies demonstrated that melatonin enhanced RAC1 activity, resulting in increased phagocytosis of apoptotic germ cells by Sertoli cells. In addition, melatonin restored gap junctions and tight junctions after heat stress, thereby promoting hollow seminiferous tubule filling. DISCUSSION: Long-term melatonin administration accelerated testicular recovery after heat stress by enhancing the phagocytotic activity of Sertoli cells and the regeneration of spermatogenic cells. This finding suggests that melatonin is a potential therapeutic for heat stress-induced male infertility.

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits.

The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

The hornwort genome and early land plant evolution.

Hornworts, liverworts and mosses are three early diverging clades of land plants, and together comprise the bryophytes. Here, we report the draft genome sequence of the hornwort Anthoceros angustus. Phylogenomic inferences confirm the monophyly of bryophytes, with hornworts sister to liverworts and mosses. The simple morphology of hornworts correlates with low genetic redundancy in plant body plan, while the basic transcriptional regulation toolkit for plant development has already been established in this early land plant lineage. Although the Anthoceros genome is small and characterized by minimal redundancy, expansions are observed in gene families related to RNA editing, UV protection and desiccation tolerance. The genome of A. angustus bears the signatures of horizontally transferred genes from bacteria and fungi, in particular of genes operating in stress-response and metabolic pathways. Our study provides insight into the unique features of hornworts and their molecular adaptations to live on land.

Drinking Warm Water Improves Growth Performance and Optimizes the Gut Microbiota in Early Postweaning Rabbits during Winter.

Accumulating evidence indicates that cold exposure changes the composition of the gut microbiota and reduces intestinal immunity in early postweaning livestock. However, little is known about the effects of drinking warm water (WW) on gut microbiota during winter. In this study, we investigated the effects of drinking WW in winter on the growth performance and gut microbiota structure of rabbits raised in poorly insulated housing from the early postweaning period (day 46) to the subadult period (day 82). The average daily gain and feed conversion ratio in rabbits drinking WW were significantly improved compared to those of the rabbits drinking cold water (CW) during 47-58 days. In addition, rabbits drinking WW had a significantly decreased the risk of diarrhea during 71-82 days. 16S rRNA sequence analysis revealed that the alpha diversity of the cecal microbiota was not significantly different between the WW and CW groups, but significantly increased with age. The relative abundance of cecal microorganisms, such as Coprococcus spp. was considerably increased at day 70 in the group drinking WW. Correlation analysis indicated that Coprococcus spp. was negatively associated with pro-inflammatory factors. In conclusion, our results suggest that drinking WW has a positive effect on growth performance and gut microbiota in rabbits during the early postweaning stage in winter.

MiR-137 suppresses tumor growth and metastasis in clear cell renal cell carcinoma.

BACKGROUND: The most frequent type of renal cell carcinoma is called clear-cell renal cell carcinoma (ccRCC) which is associated with a poor prognosis. It has been observed that miR-137 is aberrantly expressed in many different kinds of human malignancies including ccRCC. This research aims to examine the role of miR-137 in ccRCC. METHODS: Quantitative RT-PCR (qRT-PCR) was applied to measure miR-137 expression in ccRCC and adjacent noncancerous tissue. Gene expression was determined by western blot. Cell Counting Kit-8 (CCK-8) assay, flow cytometry and Transwell assay were used to determine the effects of miR-137 on cell growth, apoptosis and invasion, respectively. Moreover, xenograft and pulmonary metastasis animal models were established to investigate the role of miR-137 in vivo. RESULTS: Our findings show that there was significant downregulation of miR-137 in ccRCC tissue relative to corresponding non-cancerous tissue. Ectopic miR-137 expression in ccRCC cells led to suppression of cell growth and invasion, as well as apoptosis induction. In contrast, knockdown of miR-137 enhances proliferation and invasion, inhibits apoptosis. It also confirms that miR-137 plays a tumor supressor role in vivo. Mechanically, miR-137 directly targets the 3'-UTR of RLIP76 which is an established oncogene in ccRCC. CONCLUSION: MiR-137 serves as a tumor suppressor, which can be considered a potential therapeutic target in ccRCC.

Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis.

Oleanolic acid (3ß-hydroxyolean-12-en-28-oic acid, OA) is a naturally-occurring triterpenoid with various promising pharmacological properties. The present study was conducted to determine the protective effects of OA against oxidized low-density lipoprotein (ox-LDL) induced endothelial cell apoptosis and the possible underlying mechanisms. Our results showed that ox-LDL significantly decreased cell viability and induced apoptosis in human umbilical vein endothelial cells (HUVECs). OA in the co-treatment showed a protective effect against ox-LDL induced loss in cell viability and an increase in apoptosis, which was associated with the modulating effect of OA on ox-LDL induced hypoxia-inducible factor 1α(HIF-1α) expression. Moreover, our results showed that the modulating effect of OA against ox-LDL induced HIF-1α expression was obtained via inhibition of lipoprotein receptor 1 (LOX-1)/reactive oxygen species (ROS) signaling. Collectively, we suggested that the protective effect of OA against ox-LDL induced HUVEC apoptosis might, at least in part, be obtained via inhibition of the LOX-1/ROS/HIF-1α signaling pathway.

Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections.

Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5-C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.