Spatiotemporal transcriptomic atlas of rhizome formation in Oryza longistaminata.

Rhizomes are modified stems that grow underground and produce new individuals genetically identical to the mother plant. Recently, a breakthrough has been made in efforts to convert annual grains into perennial ones by utilizing wild rhizomatous species as donors, yet the developmental biology of this organ is rarely studied. Oryza longistaminata, a wild rice species featuring strong rhizomes, provides a valuable model for exploration of rhizome development. Here, we first assembled a double-haplotype genome of O. longistaminata, which displays a 48-fold improvement in contiguity compared to the previously published assembly. Furthermore, spatiotemporal transcriptomics was performed to obtain the expression profiles of different tissues in O. longistaminata rhizomes and tillers. Two spatially reciprocal cell clusters, the vascular bundle 2 cluster and the parenchyma 2 cluster, were determined to be the primary distinctions between the rhizomes and tillers. We also captured meristem initiation cells in the sunken area of parenchyma located at the base of internodes, which is the starting point for rhizome initiation. Trajectory analysis further indicated that the rhizome is regenerated through de novo generation. Collectively, these analyses revealed a spatiotemporal transcriptional transition underlying the rhizome initiation, providing a valuable resource for future perennial crop breeding.

The discovery and utilization of favorable genes in Oryza longistaminata.

Asian cultivated rice has been domesticated from ancestors of the wild rice species Oryza rufipogon. During this process, important changes have occurred in many agronomic traits, such as plant height, grain shattering, and panicle shape, and the yield has also greatly increased. However, many favored traits (e.g., stress resistance) have been lost. The genome of O. longistaminata is of the same AA type as O. sativa, harboring many genes conferring resistance to biotic and abiotic stresses, and it is considered as a potential gene pool for genetic improvement of O. sativa. In this review, we summarize the basic research on O. longistaminata, including its resistance to biotic and abiotic stresses, its rhizome traits, and other traits that are of potential application value, such as bacterial blight resistance, drought resistance, heat tolerance, self-incompatibility, nitrogen efficiency, and high yield. Furthermore, we present the current applied research progress on perennial rice breeding based on the rhizome trait of O. longistaminata. Lastly, the possibility of de novo domestication of O. longistaminata is discussed. We expect this article to provide information to enhance the basic research of O. longistaminata and accelerate the genetic improvement of cultivated rice.

Endovascular intervention vs. microsurgery on the prognosis of anterior circulation blood blister-like aneurysm: A cohort study.

Background: There are no universally acknowledged standardized treatment strategies for blood blister-like aneurysms (BBAs). This study compared the prognosis of patients with BBA who underwent craniotomy microsurgery vs. endovascular intervention. Methods: This retrospective cohort study included patients with BBA treated between September 2009 and August 2020 at Sichuan Provincial People's Hospital affiliated to the Sichuan Academy of Medical Science. Patients were divided into the microsurgery and endovascular groups. The preoperative Hunt-Hess grade and modified Fisher grade were collected. The intraoperative and postoperative complications (including intraoperative aneurysm rupture and hemorrhage, postoperative cerebral hemorrhage, and BBA recurrence) were recorded. Results: Seventy-two patients were included: 28 and 44 in the microsurgery and endovascular groups, respectively. Only the preoperative Fisher grade was different between the two groups (P = 0.041). The proportion of patients with good outcomes was lower in the microsurgery group (28.6%) than in the endovascular group (72.7%), and the mortality rate was higher in the microsurgery group (32.1%) than in the endovascular group (11.4%) (P < 0.05). After adjustment for the modified Fisher grade, the multivariable analysis showed that compared with craniotomy microsurgery, an endovascular intervention was associated with the prognosis of patients with BBA (OR = 0.128, 95%CI: 0.040-0.415, P < 0.001). The rate of complications (intraoperative hemorrhage, cerebral infarction, and recurrence) was higher in the microsurgery group than in the endovascular group. Conclusion: In patients with BBA, an endovascular intervention appears to be associated with a better prognosis compared with craniotomy microsurgery.

Regeneration pattern and genome-wide transcription profile of rhizome axillary buds after perennial rice harvest.

Perennial rice is a new type of rice that allows the harvest of rice for multiple years without growing new seedlings annually. This technology represents a green and sustainable agricultural production mode with many advantages for balancing agricultural ecology and food security. However, the differences in regeneration patterns between perennial and annual rice and the gene regulatory pathways of the apical dominance in axillary bud growth after harvest in perennial rice are still unclear. In this study, perennial rice (PR23) and annual rice (Chugeng28) were used to investigate axillary bud growth patterns before and after apical spike removal. After elimination of apical dominance at different development stages, perennial rice rhizome axillary buds at the compression nodes germinated more rapidly than others and developed into new seedlings. The axillary buds at the high-position nodes in annual rice grew faster than those at other nodes. Furthermore, the global gene expression patterns of PR23 rhizome buds at compression nodes grown for 1, 3, 4, and 5 days after apical spike removal were analyzed by transcriptome sequencing. Compared with the control buds without apical removal, 264, 3,484, 2,095, and 3,398 genes were up-regulated, and 674, 3,484, 1,594, and 1,824 genes were down-regulated in the buds grown for 1, 3, 4, and 5 days after apical spike removal, respectively. Trend analysis of the expressed genes at different time points was performed and co-expression network was constructed to identify key genes in rhizome axillary bud regrowth. The results showed that 85 hub genes involved in 12 co-regulatory networks were mainly enriched in the light system, photosynthesis-antenna protein, plant hormone signal transduction, ABC transporter and metabolic pathways, which suggested that hormone and photosynthetic signals might play important roles in the regulation of rhizome axillary bud regeneration in perennial rice. Overall, this study clarified the differences in the regeneration patterns of axillary buds between perennial and annual rice and provided insight into the complex regulatory networks during the regeneration of rhizome axillary buds in perennial rice.

A Genetic Network Underlying Rhizome Development in Oryza longistaminata.

The rhizome is an important organ through which many perennial plants are able to propagate vegetatively. Its ecological role has been thoroughly studied on many grass species while the underlying genetic basis is mainly investigated using a rhizomatous wild rice species-Oryza longistaminata. Previous studies have revealed that the rhizome trait in O. longistaminata is jointly controlled by multiple loci, yet how these loci interact with each other remains elusive. Here, an F2 population derived from Oryza sativa (RD23) and O. longistaminata was used to map loci that affect rhizome-related traits. We identified 13 major-effect loci that may jointly control rhizomatousness in O. longistaminata and a total of 51 quantitative trait loci (QTLs) were identified to affect rhizome abundance. Notably, some of these loci were found to have effects on more than one rhizome-related trait. For each trait, a genetic network was constructed according to the genetic expectations of the identified loci. Furthermore, to gain an overview of the genetic regulation on rhizome development, a comprehensive network integrating all these individual networks was assembled. This network consists of three subnetworks that control different aspects of rhizome expression. Judging from the nodes' role in the network and their corresponding traits, we speculated that qRHZ-3-1, qRHZ-4, qRHI-2, and qRHI-5 are the key loci for rhizome development. Functional verification using rhizome-free recombinant inbred lines (RILs) suggested that qRHI-2 and qRHI-5, two multi-trait controlling loci that appeared to be critical in our network analyses, are likely both needed for rhizome formation. Our results provide more insights into the genetic basis of rhizome development and may facilitate identification of key rhizome-related genes.

Confirmation of a Gametophytic Self-Incompatibility in Oryza longistaminata.

Oryza longistaminata, a wild species of African origin, has been reported to exhibit self-incompatibility (SI). However, the genetic pattern of its SI remained unknown. In this study, we conducted self-pollination and reciprocal cross-pollination experiments to verify that O. longistaminata is a strictly self-incompatible species. The staining of pollen with aniline blue following self-pollination revealed that although pollen could germinate on the stigma, the pollen tube was unable to enter the style to complete pollination, thereby resulting in gametophytic self-incompatibility (GSI). LpSDUF247, a S-locus male determinant in the gametophytic SI system of perennial ryegrass, is predicted to encode a DUF247 protein. On the basic of chromosome alignment with LpSDUF247, we identified OlSS1 and OlSS2 as Self-Incompatibility Stamen candidate genes in O. longistaminata. Chromosome segment analysis revealed that the Self-Incompatibility Pistil candidate gene of O. longistaminata (OlSP) is a polymorphic gene located in a region flanking OlSS1. OlSS1 was expressed mainly in the stamens, whereas OlSS2 was expressed in both the stamens and pistils. OlSP was specifically highly expressed in the pistils, as revealed by RT-PCR and qRT-PCR analyses. Collectively, our observations indicate the occurrence of GSI in O. longistaminata and that this process is potentially controlled by OlSS1, OlSS2, and OlSP. These findings provide further insights into the genetic mechanisms underlying self-compatibility in plants.

Identification of Key Genes for the Ultrahigh Yield of Rice Using Dynamic Cross-tissue Network Analysis.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candidate high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/ztpub/DCT.

Evolution of Plant Architecture in Oryza Driven by the PROG1 Locus.

The genetic control of plant architecture in crops is critical for agriculture and understanding morphological evolution. This study showed that an open reading frame (ORF) of the rice domestication gene PROG1 appeared 3.4-3.9 million years ago (Mya). Subsequently, it acquired a novel protein-coding gene function in the genome of O. rufipogon (~0.3-0.4 Mya). This extremely young gene and its paralogous C2H2 genes located nearby define the prostrate architecture of O. rufipogon and, thus, are of adaptive significance for wild rice in swamp and water areas. However, selection for dense planting and high yield during rice domestication silenced the PROG1 gene and caused the loss of the RPAD locus containing functional C2H2 paralogs; hence, domesticated lines exhibit an erect plant architecture. Analysis of the stepwise origination process of PROG1 and its evolutionary genetics revealed that this zinc-finger coding gene may have rapidly evolved under positive selection and promoted the transition from non- or semi-prostrate growth to prostrate growth. A transgenic assay showed that PROG1 from O. rufipogon exerts a stronger function compared with PROG1 sequences from other Oryza species. However, the analysis of the expression levels of PROG1 in different Oryza species suggests that the transcriptional regulation of PROG1 has played an important role in its evolution. This study provides the first strong case showing how a fundamental morphological trait evolved in Oryza species driven by a gene locus.

Neo-functionalization of a Teosinte branched 1 homologue mediates adaptations of upland rice.

The rice orthologue of maize domestication gene Teosinte branched 1 (Tb1) affects tillering. But, unlike maize Tb1 gene, it was not selected during domestication. Here, we report that an OsTb1 duplicate gene (OsTb2) has been artificially selected during upland rice adaptation and that natural variation in OsTb2 is associated with tiller number. Interestingly, transgenic rice overexpressing this gene shows increased rather than decreased tillering, suggesting that OsTb2 gains a regulatory effect opposite to that of OsTb1 following duplication. Functional analyses suggest that the OsTb2 protein positively regulates tillering by interacting with the homologous OsTb1 protein and counteracts the inhibitory effect of OsTb1 on tillering. We further characterize two functional variations within OsTb2 that regulate protein function and gene expression, respectively. These results not only present an example of neo-functionalization that generates an opposite function following duplication but also suggest that the Tb1 homologue has been selected in upland rice.

SOX2 mediates crosstalk between Sonic Hedgehog and the Wnt/ß-catenin signaling pathway to promote proliferation of pituitary adenoma cells.

The Sonic hedgehog (Shh) and Wnt/ß-catenin signaling pathways are important regulators of early tissue patterning and stem cell propagation, and aberrant regulation of these two signaling pathways has been associated with a number of types of cancer. The identification of adult stem cells in the pituitary raised the question of whether these two signaling pathways are involved in pituitary adenoma formation. In the present study, it was identified that treating a human pituitary adenoma cell line with Shh was not able to promote the proliferation of cancer cells, but Shh was able to upregulate the expression of sex-determining region Y box 2 (SOX2) which is characteristic of stem cells. The addition of Shh into ß-catenin-expressing cells also promoted cell proliferation. On the other hand, addition of Wnt3a into or overexpression of ß-catenin in SOX2-expressing cancer cells was able to promote cell proliferation, Further investigation revealed that SOX2 is required to mediate crosstalk between the Shh and Wnt/ß-catenin signaling pathways to promote the proliferation of pituitary adenoma cells.

Deep Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous Malformations.

BACKGROUND: Deregulation of circulating microRNAs (miRNAs) is always associated with development and progression of human diseases. We aimed to assess whether patients with brain arteriovenous malformations (BAVMs) possess a distinct miRNA signature compared with healthy subjects. METHODS: Three patients with unruptured BAVMs and 3 normal control subjects were recruited as case and control groups. Peripheral blood was collected, and miRNA signature was obtained by next-generation sequencing, followed by comparative, functional, and network analyses. Quantitative reverse transcription polymerase chain reaction was performed to validate expression of specific miRNAs. RESULTS: Deep sequencing detected 246 differentially expressed miRNAs in blood samples of patients with BAVMs compared with normal control subjects. For the top 5 miRNAs, 946 target genes were predicted, and a BAVM-specific miRNA-target gene regulatory network was constructed. Functional annotation suggested that 15 of the predicted miRNA-targeted genes were involved in vascular endothelial growth factor signaling, in which 3 critical miRNAs were involved: miR-7-5p, miR-199a-5p, and miR-200b-3p. CONCLUSIONS: We explored the miRNA expression signature of BAVMs, which will provide an important foundation for future studies on the regulation of miRNAs involved in BAVMs.

DLK silencing attenuated neuron apoptosis through JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.

OBJECTIVE: Dual leucine zipper kinase (DLK/MA3K12) has been reported involved in apoptosis and neuronal degeneration during neural development and traumatic brain injury. This study was designed to investigate the role of DLK with its adaptor protein JNK interacting protein-3 (JIP3), and its downstream MA2K7/JNK signaling pathway in early brain injury (EBI) after subarachnoid hemorrhage (SAH) in a rat model. DESIGN: Controlled in vivo laboratory study. SETTING: Animal research laboratory. SUBJECTS: Two hundred and twenty-three adult male Sprague-Dawley rats weighing 280-320g. INTERVENTIONS: SAH was induced by endovascular perforation in rats. The SAH grade, neurological score, and brain water content were measured at 24 and 72h after SAH. Immunofluorescence staining was used to detect the cells that expressed DLK. The terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to detect the neuronal apoptosis. In mechanism research, the expression of DLK, JIP3, phosphorylated-JNK (p-JNK)/JNK, and cleaved caspase-3 (CC-3) were analyzed by western blot at 24h after SAH. The DLK small interfering RNA (siRNA), JIP3 siRNA, MA2K7 siRNA and recombinant DLK protein which injected intracerebroventricularly were given as the interventions. MEASUREMENTS AND MAIN RESULTS: The DLK expression was increased in the left cortex neurons and peaked at 24h after SAH. DLK siRNA attenuated brain edema, reduced neuronal apoptosis, and improved the neurobehavioral functions after SAH, but the recombinant DLK protein deteriorated neurobehavioral functions and brain edema. DLK siRNA decreased and recombinant DLK protein increased the expression of MA2K7/p-JNK/CC-3 at 24h after SAH. The JIP3 siRNA reduced the level of JIP3/MA2K7/p-JNK/CC-3, combined DLK siRNA and JIP3 siRNA further decreased the expression of DLK/MA2K7/p-JNK/CC-3, and MA2K7 siRNA lowered the amount of MA2K7/p-JNK/CC-3 at 24h after SAH. CONCLUSIONS: As a negative role, DLK was involved in EBI after SAH, possibly mediated by its adaptor protein JIP3 and MA2K7/JNK signaling pathways. To reduce the level of DLK may be a new target as intervention for SAH.

The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP.

Long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be involved in the development and progression of many types of tumors including breast cancer, gastric cancer, and bladder cancer. However, the exact effects and molecular mechanisms of UCA1 in glioma progression remain unclear up to now. In this study, we firstly found that UCA1 was upregulated in glioma tumor samples and negatively correlated with survival time. Then, we investigated the role of UCA1 in human glioma cell lines. Our results showed that upregulation of lncRNA-UCA1 in glioma tissues and cell lines could promote glioma cell proliferation and migration through interaction with miR-182, and knockdown of UCA1 inhibited the proliferation and migration of human glioma cell. In addition, miR-182 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) was required in the regulation of UCA1 induced glioma cell proliferation. Taken together, UCA1 might promote proliferation and migration of glioma, to regulate the tumor growth and metastasis via miR-182 dependent iASPP regulation. Therefore, lncRNA-UCA1 could be regarded as a therapeutic target in human glioma.

Global Gene Expression Patterns and Somatic Mutations in Sporadic Intracranial Aneurysms.

BACKGROUND: High-throughput sequencing technologies can expand our understanding of the pathologic basis of intracranial aneurysms (IAs). Our study was aimed to decipher the gene expression signature and genetic factors associated with IAs. METHODS: We determined the gene expression levels of 3 cases of IAs by RNA sequencing. Bioinformatics analysis was conducted to identify the differentially expressed genes (DEGs) and uncover their biological function. In addition, whole genome sequencing was performed on an additional 6 cases of IAs to detect the potential somatic alterations in DEGs. RESULTS: Compared with the normal arterial tissue, 1709 genes were differentially expressed in IAs arterial tissue. The most significantly up-regulated gene and down-regulated gene, H19 and HIST1H3J, may be essential for tumorigenesis of IAs. Hub protein of IKBKG in protein-protein interaction network was probably involved in the inflammation process in aneurysms. Another 2 hub proteins, ACTB and MKI67IP, as well as up-regulated genes, might be abnormally activated in aneurysms and involved in the pathogenesis of IAs. Further whole genome sequencing and filtering yielded 4 candidate somatic single nucleotide variants including MUC3B, and BLM may be involved in the pathogenesis of IAs. Even though, our results do not support the hypothesis of somatic mutations occurred in the DEGs. CONCLUSIONS: Two-dimensional genomic data from transcriptome and whole genome sequencing indicated that no somatic mutations occurred in DEGs. In addition, 3 DEGs (IKBKG, ACTB, and MKI67IP) and 2 mutant genes (MUC3B and BLM) were essential in IAs.

Disposal of Occipital Condyle in Far Lateral Approach for Ventrolateral Foramen Magnum Meningiomas.

OBJECTIVE: To investigate the necessity of drilling the occipital condyle in a tailored far lateral approach for resection of ventrolateral foramen magnum meningiomas (FMMs). METHODS: Clinical data of 15 patients with ventrolateral FMMs who underwent surgery during a 6-year period were reviewed retrospectively. RESULTS: A retrocondylar approach was performed in 8 cases (6 above the vertebral artery [VA] and 2 below the VA) in which the dural attachment was surgically accessible with no restriction of the initial part of the V4 segment of the VA, and a partial transcondylar approach was performed in 7 cases on both sides of the VA where the dural attachment associated with the VA auxiliary space was reached by superolateral displacement of the VA by drilling of the condyle. Exposure of the V3 segment of the VA was performed in all patients, but no circumcision of the dural ring along with transposition of the VA was needed. Simpson grade II resection was achieved in all patients. Postoperative complications were encountered in 20% of patients, predominantly associated with cranial nerve impairment. No tumor recurrence was demonstrated during follow-up lasting 7-68 months (mean 29.2 months). CONCLUSIONS: The surgical approach for ventrolateral FMMs varies depending on the location of dural attachment with reference to VA dural entry. Bone removal is warranted in FMMs arising from both sides of the VA to allow superolateral displacement of the VA to some extent, improving surgical accessibility to the hidden VA auxiliary space and achieving a more radical tumor resection. It should be a reasonable alternative to the conventional aggressive VA transposition in cases of ventrolateral FMMs.

Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.

BACKGROUND AND PURPOSE: Since tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred sixteen (216) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 h after SAH. Dual leucine zipper kinase (DLK) and its downstream factors, JNK-interacting protein 3 (JIP3), MA2K7, p-JNK/JNK (c-Jun N-terminal kinase), and apoptosis related proteins cleaved caspase-3 (CC-3), Bim, Bcl-2, and cleaved caspase-9 (CC-9) were analyzed by western blot at 24 h after SAH. Apoptotic cells were detected by terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). DLK small interfering RNA (siRNA), JIP3 siRNA and MA2K7 siRNA, the JNK, p38MAPK, and MEK inhibitors SP600125, SB203580, and PD98059 were used for intervention. RESULTS: Tozasertib reduced neuronal apoptosis, attenuated brain edema and improved neurobehavioral deficits 24 and 72 h after SAH. At 24 h After SAH, DLK/JIP3/MA2K7/p-JNK/CC-3 expressions were elevated markedly and tozasertib reduced DLK, MA2K7/p-JNK/CC-3 expressions but enhanced JIP3 expression. In the presence of tozasertib, DLK/JIP3/MA2K7 siRNA and SP600125, SB203580 and PD98059 deteriorated the neurobehavioral deficits, brain edema and increased the expression of CC-3. SAH potentiated the expression of Bim, CC-9, and CC-3 but reduced Bcl-2, while tozasertib reduced expression of Bim, CC-9, and CC-3 but enhanced Bcl-2. CONCLUSIONS: Tozasertib reduced neuronal apoptosis and improved outcome possibly via DLK/JIP3/MA2K7/JNK pathways after SAH.

Intraoperative Combined Use of Somatosensory Evoked Potential, Microvascular Doppler Sonography, and Indocyanine Green Angiography in Clipping of Intracranial Aneurysm.

BACKGROUND The aim of this study was to evaluate the effect of combining application of somatosensory evoked potential (SEP), microvascular Doppler sonography (MDS), and indocyanine green angiography (ICGA) in intracranial aneurysm clipping surgery. MATERIAL AND METHODS A total of 158 patients undergoing an intracranial aneurysm clipping operation were recruited. All patients were evaluated with intraoperative SEP and MDS monitoring, and 28 of them were evaluated with intraoperative combined monitoring of SEP, MDS, and ICGA. RESULTS The SEP waves dropped during temporary occlusion of arteries in 19 cases (12.0%), and returned to normal after the clips were repositioned. After aneurysms were clipped, the vortex flow signals were detected by MDS in 6 cases. The aneurysm neck remnants were detected by ICGA in 2 cases of olfactory artery (OA) and in 1 case of middle cerebral artery (MCA), which disappeared after the clips were repositioned. Postoperative CTA or DSA showed that aneurysms were clipped completely and parent arteries and perforating vessels were patent. GOS at 1 month after the surgery was good in 111 cases (70.3%), mild disability in 22 cases (13.9%), severe disability in 14 cases (8.9%), vegetative state in 5 cases (3.2%), and death in 6 cases (3.8%). CONCLUSIONS Intraoperative combining application of SEP, MDS, and ICGA can reduce brain tissue ischemia and damage and disability and mortality rate after effective clipping of intracranial aneurysms, thereby improving surgical outcomes.

Gossypol acetate induced apoptosis of pituitary tumor cells by targeting the BCL-2 via the upregulated microRNA miR-15a.

It is reported that gossypol acetate (GAA) has obvious effects on inhibiting the growth of tumors, by inhibiting the activity of enzymes. Ultrastructural study showed that GAA can cause morphological changes of mitochondria which leads to the apoptosis of tumors. However, little is known about the pathways that how the GAA triggers apoptosis of tumors and what kind of the molecular events have happened when GAA is added. The aim of the study is try to know if GAA have some functions on pituitary tumor cell. And if there are any changes after GAA treatment, we try to understand the mechanisms that how GAA regulate the growth of pituitary tumor cell. The study was carried out on rat lactotroph cell lines, GH3 and MMQ. Q-PCR and western blot (WB) assay are used to determine the expression level of genes and the protein level. Both the miR-15a (mimics) overexpression cell line and miR-15a knock out (inhibitor) cell line were obtained in GH3 and MMQ. Apoptosis rate was determined by flow cytometry (FCM). Our study revealed that: 1) GAA inhibits the proliferation of pituitary tumor cells of GH3, MMQ. 2) GAA upregulate the expression of miR15a in GH3 and MMQ. 3) Overexpressed miR-15a (mimics) downregulates the expression level of Bcl-2. 4) Knock down miR-15a (inhibitor) upregulates Bcl-2 and reverse the apoptosis induced by GAA. Our study indicates that GAA-induced decrease in cell proliferation is associated with decreased expression of Bcl-2 and increased miR-15a. Based on this, we propose developing GAA as a novel therapeutic tool in the management of pituitary tumor.

A retrospective comparison of the influence of surgical clipping and endovascular embolization on recovery of oculomotor nerve palsy in patients with posterior communicating artery aneurysms.

BACKGROUND: Oculomotor nerve palsy (ONP) is a common symptom of posterior communicating artery aneurysms (PcomAAs). Surgical clipping and endovascular embolization are used to treat PcomAAs with ONP. OBJECTIVE: To analyze the impact of these 2 techniques on recovery of ONP caused by PcomAAs. METHODS: The clinical data for 176 patients with intracranial PcomAAs with ONP admitted to the Department of Neurosurgery, Sichuan Provincial People's Hospital, between June 2008 and May 2013 who undergone surgical clipping or endovascular embolization were studied retrospectively. The 2 treatment groups were compared with respect to age, sex, aneurysm size, levels of hypertension and hyperlipidemia, preadmission ONP duration, subarachnoid hemorrhage (SAH), complete ONP, postoperative recovery time from ONP symptoms, and degree of recovery. The follow-up duration was a minimum of 12 months. Multivariate Cox regression was used for analysis. RESULTS: A total of 132 patients were treated by surgical clipping, and 44 were treated by endovascular embolization. Significant differences were found in postoperative recovery time (83.87 ± 34.70 days for clipping and 137.45 ± 44.94 days for embolization, P < .001) and recovery rates (130 [98.5%] for clipping and 30 [68.2%] for embolization, P < .001). The period between ONP onset and admission was associated with recovery. Postoperative complications included significant cerebral vasospasms (6 in the clipping group and 2 in the embolization group) and hydrocephalus (16 in the clipping group and 9 in the embolization group). CONCLUSION: Simultaneous elimination of 2 injury mechanisms, compression and pulsation, when treating the oculomotor nerve by surgical clipping may be more advantageous than endovascular embolization to treat ONP caused by PcomAA.