Middle cerebral artery bifurcation aneurysms are associated with patient age, sex, bifurcation angle, and vascular diameters.

To investigate the relationship of the middle cerebral artery (MCA) bifurcation aneurysms with patients' age and sex, vascular angles at the bifurcation, and diameters of the M1 and two M2 arteries, patients with and without MCA aneurysms were retrospectively enrolled. The lateral angles, MCA bifurcation angle and arterial diameter were measured and analyzed. Totally, 121 (19.0%) patients with and 517 (81.0%) without MCA aneurysms were enrolled. Most (n = 88 or 72.7%) aneurysms were present in the age range of 40-70 years, and significantly (P = 0.01) more women than men had the bifurcation aneurysms. The MCA bifurcation angle was significantly greater (149.2° ± 32.6° vs. 107.2° ± 26.3°; P < 0.0001) while both the smaller and larger lateral (M1/M2) angles were significantly smaller in patients with than without aneurysms (82.0° ± 23.7° vs. 109.1° ± 22.7° with P < 0.001 for the smaller and 123.2° ± 25.2° vs. 139.5° ± 16.9° with P < 0.001 for the larger lateral angle). 109 (90.1%) bifurcation aneurysms deviated towards the smaller lateral angle, and 103 (85.1%) aneurysms deviated towards the thinner M2 branch. The maximal aneurysm diameter ranged 1.6-13.8 (mean 5.4 ± 2.4) mm and was significantly (P < 0.05) positively correlated with the diameter of both M2 arterial branches (R = 0.57 and P = 0.01 for the smaller M2, and R = 0.69 and P = 0.002 for the larger M2) or the MCA bifurcation angle. A significant (P < 0.0001) negative correlation was detected between age and the smaller lateral angle but a significant (P < 0.0001) positive correlation between age and the MCA bifurcation angle in patients without MCA bifurcation aneurysms or in the total patients. MCA bifurcation angle was the only significant (P = 0.0001, odds ratio 2.7, 95% confidence interval 1.6-3.8) independent risk factor for MCA bifurcation aneurysm presence, with the bifurcation angle threshold of 124.1° and an area under the ROC curve of 0.86. In conclusion, significantly more MCA bifurcation aneurysms are present in older patients, females, and patients with a wider MCA bifurcation angle, and deviate towards the smaller lateral angle and the thinner M2 segment. MCA bifurcation angle is the only independent risk factor for presence of MCA bifurcation aneurysms with the threshold of 124.1°.

Dynamic RBM47 ISGylation confers broad immunoprotection against lung injury and tumorigenesis via TSC22D3 downregulation.

ISGylation is a well-established antiviral mechanism, but its specific function in immune and tissue homeostasis regulation remains elusive. Here, we reveal that the RNA-binding protein RBM47 undergoes phosphorylation-dependent ISGylation at lysine 329 to regulate immune activation and maintain lung homeostasis. K329R knockin (KI) mice with defective RBM47-ISGylation display heightened susceptibility to LPS-induced acute lung injury and lung tumorigenesis, accompanied with multifaceted immunosuppression characterized by elevated pro-inflammatory factors, reduced IFNs/related chemokines, increased myeloid-derived suppressor cells, and impaired tertiary lymphoid structures. Mechanistically, RBM47-ISGylation regulation of the expression of TSC22D3 mRNA, a glucocorticoid-inducible transcription factor, partially accounts for the effects of RBM47-ISGylation deficiency due to its broad immunosuppressive activity. We further demonstrate the direct inhibitory effect of RBM47-ISGylation on TSC22D3 expression in human cells using a nanobody-targeted E3 ligase to induce site-specific ISGylation. Furthermore, epinephrine-induced S309 phosphorylation primes RBM47-ISGylation, with epinephrine treatment exacerbating dysregulated cytokine expression and ALI induction in K329R KI mice. Our findings provide mechanistic insights into the dynamic regulation of RBM47-ISGylation in supporting immune activation and maintaining lung homeostasis.

Use of the Neuroform Atlas stent for wide-necked cerebral aneurysms.

To investigate the effect and safety of the Neuroform Atlas (NFA) stent in stent-assisted coiling of wide-necked intracranial aneurysms, patients with wide-necked intracranial aneurysms were retrospectively enrolled and treated with the NFA stent-assisted coiling. The modified Rankin scale (mRS) grades and Raymond grades were used to assess the clinical outcomes and aneurysm occlusion degrees, respectively, after embolization and at follow-up. Totally, 122 patients were enrolled with 129 wide-necked aneurysms, and forty-nine (40.2%) patients experienced subarachnoid hemorrhage. A total of 134 NFA stents were deployed in all patients. Immediately after endovascular embolization, the Raymond grade was I in 112 (86.8%), II in 8 (6.2%), and III in 9 (7.0%). Complications occurred in 7 (5.7%) patients, including stent displacement in 2 (1.6%) patients, thrombosis and cerebral infarction in 4 (3.3%), and death in 1 (0.8%). Clinical follow-up was performed in 113 (92.6%) patients 6-30 (mean 21) months after embolization, with the mRS grade 0 in 99 (87.6%) patients, 1 in 7 (6.2%), 2 in 5 (4.4%), and 3 in 2 (1.8%). Good prognosis (mRS ≤ 2) was achieved in 111 (98.2%) patients while poor prognosis (mRS > 2) in two (1.8%). Digital subtraction angiography was conducted in 98 (80.3%) patients with 104 (80.6%) aneurysms 6-30 (mean 21) months after embolization. The Raymond grade was grade I in 94 (90.4%) aneurysms, II in 4 (3.8%), and III in 6 (5.8%). Compared with the Raymond grades immediately after embolization, 93 (89.4%) aneurysms disappeared, 9 (8.7%) remained unchanged in the occlusion status, and 2 (1.9%) were recurrent. In conclusion, the NFA stent may have a high aneurysm occlusion rate and a low complication rate in assisting coiling of wide-necked intracranial aneurysms even though further studies are necessary to prove this.

Effects of endovascular recanalization on symptomatic non-acute occlusion of intracranial arteries.

To investigate the effect and safety of recanalization surgery for non-acute occlusion of large intracranial arteries and factors affecting clincial outcomes. Patients with non-acute occlusion of internal carotid artery (ICA), middle cerebral artery (MCA), and vertebrobasilar artery (VBA) treated with recanalization were retrospectively enrolled. The clinical and angiographic data were analyzed. 177 patients were enrolled, including 67 patients with intracranial ICA occlusion, 52 with MCA occlusion, and 58 with VBA occlusion. Successful recanalization was achieved in 152 (85.9%) patients. Complications occurred in 15 patients (8.5%). Followed up for 3-7 months, the 90 day mRS was significantly improved compared with that before the procedure. Among 152 patients with successful recanalization, eight patients experienced reocclusion (5.3%), and 11 patients experienced restenosis (7.2%). Successful recanalization was significantly (P < 0.05) associated with occlusion duration, calcification or angulation of the occluded segment. Complications were significantly (P < 0.05) associated with location of occlusion, hyperlipidemia, and patients' height. Restentosis or reocclusion at follow-up was significantly (P < 0.05) associated with complications and mRS at 90 days. The significant (P < 0.05) independent risk factors were angulation and calcification for successful recanalization, hyperlipidemia for complications, and mRS at 90 days for restenosis or reocclusion at follow-up. Recanalization surgery may be a safe and effective approach for patients with non-acute symptomatic occlusion of large intracranial arteries, and factors significantly independently associated with successful recanalization, periprocedural complications and restenosis or reocclusion after surgery have been identified for future reference to improve clinical outcomes.

Sub-satisfactory recanalization of severe middle cerebral artery stenoses can significantly improve hemodynamics.

Purpose: To investigate the effect of sub-satisfactory stent recanalization on hemodynamic stresses for severe stenoses of the middle cerebral artery (MCA) M 1 segment. Materials and methods: Patients with severe stenoses of the MCA M1 segment treated with endovascular stent angioplasty were retrospectively enrolled. Three-dimensional digital subtraction angiography before and after stenting was performed; the computational fluid dynamics (CFD) analysis of hemodynamic stresses at the stenosis and normal segments proximal and distal to the stenoses was analyzed. Results: Fifty-one patients with severe stenosis at the MCA M1 segment were enrolled, with the stenosis length ranging from 5.1 to 12.8 mm (mean 9 ± 3.3 mm). Stent angioplasty was successful in all (100%) the patients. The angiography immediately after stenting demonstrated a significant (P < 0.05) decrease in MCA stenosis after comparison with before stenting (31.4 ±12.5% vs. 87.5 ± 9.6%), with residual stenosis of 15-30% (mean 22.4 ± 3.5%). Before stenting, the total pressure was significantly higher (P < 0.0001), while the WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment proximal to the stenosis, and the total pressure, WSS, velocity, and vorticity were all significantly decreased (P < 0.0001) at the normal arterial segment distal to the stenosis compared with those at the stenosis. After sub-satisfactory stenting recanalization, all the hemodynamic stresses proximal or distal to the stenosis and at the perforator root were improved compared with those before stenting and were similar to those after virtual stenosis removal. Conclusion: Sub-satisfactory recanalization of severe MCA stenoses can significantly improve the hemodynamic status for cerebral perfusion at the stenoses.

Endovascular treatment of intracranial vertebral artery unruptured dissecting aneurysms: Comparison of flow diversion and stent-assisted coiling or stenting alone.

Purpose: To investigate the effect and safety of flow diverters in the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery in comparison with stent-assisted coiling or stenting alone. Materials and methods: Patients with unruptured dissecting intracranial aneurysms of the vertebral artery treated with the flow diverter, stent-assisted coiling, or stenting alone were retrospectively enrolled. The clinical data were analyzed and compared. Results: Twenty-five patients were enrolled in the flow diversion group and 42 patients in the stenting group. Twenty-six flow diverters were deployed in the flow diversion group. Immediate angiography revealed contrast agent retention within the aneurysm cavity in all patients. In the stenting group, 48 stents were deployed, and immediate angiographic outcome showed O'Kelly-Marotta (OKM) grade D in 18 (42.9%) aneurysms, grade C in 16 (38.1%), and grade B in 8 (19.0%). Periprocedural ischemic complications of thrombosis occurred in two (4.8%) patients and were treated with thrombolysis. In the flow diversion group, 19 (76%) patients underwent angiographic follow-up 3-46 (median 24) months after the procedure, with the OKM grade D in 11 (57.9%) patients, C in two (10.5%), and B in six (31.6%). The aneurysm recurrence rate was zero, and all diverters remained patent. Asymptomatic instent stenosis occurred in two (10.5%) patients. In seven of the ten patients with mild or moderate parent artery stenosis before the procedure who experienced angiographic follow-up, the stenosis was improved in five (71.4%) patients. In the stenting group, angiographic follow-up was carried out in 33 (78.6%) patients 6-58 months (median 34) after the procedure, with OKM grade D in 22 (66.7%) patients, grade C in five (15.2%), grade B in three (9.1%), and aneurysm recurrence (grade B, with increased contrast agent into the aneurysm cavity) in three (9.1%). Five (16.7%) patients experienced asymptomatic instent stenosis, and six of the 12 patients (50%) with parent artery stenosis were improved. Conclusion: Flow diverters with or without selective adjunctive coiling for the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery may be safe and effective with good occlusion effects not inferior to those of stent-assisted coiling and stenting alone even though the long-term effect still warrants confirmation.

Effects of carotid artery stenting on cognitive impairment in patients with severe symptomatic carotid artery stenosis.

The effect of carotid artery stenting and medication on improvement of cognitive function in patients with severe symptomatic carotid artery stenosis is unknown. To investigate the effect of stenting compared with medication alone for severe carotid atherosclerotic stenosis on cognitive impairment. Patients with carotid stenosis and cognitive impairment were prospectively randomly divided into 2 groups of stenting or medication alone. Cognitive function was evaluated with the Montreal cognitive assessment (MoCA), Mini-Mental State Examination, and Barthel Index of Activities of Daily Living (BI). Continuous data in normal distribution were tested with the t-test but with the Mann-Whitney U test if not in normal distribution. Categorical data were presented as frequency and percentages and tested with the Fisher exact test. A P value < .05 was regarded as statistical significant. Carotid artery stenting was successfully performed in all patients (100%) in the stenting group. Compared with before treatment, the Mini-Mental State Examination, MoCA and BI scores at 6 months in the medication alone group and at 1, 3, and 6 months in the stenting group were significantly (P < .005) improved. The stenting group had significantly (P < .05) better scores than the medication alone group at the same time. At 6-month follow-up, the visuospatial/executive functions (3.69 ±â€…1.42 vs 2.42 ±â€…1.23), attention (5.24 ±â€…1.52 vs 3.63 ±â€…1.47), and language (2.64 ±â€…0.71 vs 1.96 ±â€…0.69) were significantly (P < .05) improved in the stenting group compared with the medication alone group. Carotid artery stenting may significantly improve cognitive impairment and neurological function compared with medication alone in patients with severe carotid atherosclerotic stenosis concurrent with cognitive impairment.

Improved Tolerance of Artemisia ordosica to Drought Stress via Dark Septate Endophyte (DSE) Symbiosis.

Dark septate endophytes (DSEs) usually colonize plant roots, especially in stress environments. However, their relationship with plants ranges from beneficial to harmful and has remained largely uncharacterized. In the present study, 14 DSE species grouped into 11 genera were isolated from the roots of a desert plant, Artemisia ordosica, which is widely distributed in northwest China. Three dominant DSE species-Paraphoma chrysanthemicola (Pc), Alternaria chartarum (Ac), and Acrocalymma vagum (Av)-were selected and tested for their resistance to drought in vitro. Furthermore, we characterized the responses of A. ordosica under drought conditions in relation to the presence of these DSEs following inoculation. The results showed that all three strains grew well under in vitro drought stress, and the biomass of Ac and Av was significantly higher than that of the unstressed control. The effects of DSE inoculation on the growth of A. ordosica under drought stress varied according to the different DSE species but were generally beneficial. Under drought stress, Av and Pc promoted plant growth, antioxidant enzyme activity, and root development of the hosts. The Ac strain conferred obvious positive effects on the antioxidant enzyme activity of the hosts. In general, Av and Pc demonstrated better application potential for improving the drought resistance of A. ordosica.

Case Report: Double Micro-Guidewire Technique for Emergent Rescue of Proximal Stent Collapse During Recanalization of Nonacute Occlusion of Vertebral Artery.

Cerebral arteries are usually tortuous, and in the treatment of cerebrovascular diseases with stenting, a stent deployed may be collapsed at one end, leading to reduced blood flow and subsequent stent occlusion. Immediate rescuing measures should be implemented to prevent severe ischemic events. In this case report, we present a case with V4 segment occlusion of the right vertebral artery treated with endovascular stent angioplasty. An Enterprise stent deployed at the occlusion segment was collapsed at the proximal end after withdrawal of the delivery system. Immediate rescuing measures were taken by navigating a micro-guidewire through the lateral stent mesh at the proximal end into the stent lumen followed by advancing a second micro-guidewire right through the reopened proximal stent end into the stent lumen for deployment of a supporting balloon-expandable Apollo stent to prevent stent collapse. Follow-up digital subtraction angiography 6 months later demonstrated patent stents and unobstructed blood flow.

Factors affecting in-stent restenosis after angioplasty with the Enterprise stent for intracranial atherosclerotic diseases.

This study investigated factors affecting the safety and in-stent restenosis after intracranial stent angioplasty using the Enterprise stent for symptomatic intracranial atherosclerotic stenosis. Between January 2017 and March 2019, patients with intracranial atherosclerotic stenosis treated with Enterprise stent angioplasty were enrolled, including 400 patients in the modeling group and 89 patients in the validation group. The clinical factors affecting in-stent restenosis after Enterprise stent angioplasty in the modeling group were analyzed, and a logistic regression model of these factors was established and validated in the validation group. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were analyzed. In the modeling group with 400 patients, there were 410 lesions, including 360 stenotic lesions and 50 occluded lesions, with 176 (42.9%) lesions in the anterior circulation and 234 (57.1%) in the posterior circulation. Successful stenting was performed in 398 patients (99.5%). Stenosis was significantly (P < 0.05) improved after stenting compared with before stenting (27.7% ± 2.9% vs. 77.9% ± 8.0%). Periprocedural complications included ischemic stroke (3.25%), hemorrhagic stroke (0.75%), and death (0.50%), with a total periprocedural complication rate of 4.0%. The first follow-up angiography was performed in 348 (87.0%) patients with 359 lesions 3.5-14 months (mean 5.7 months) after stenting. In-stent restenosis occurred in 62 (17.3%) lesions, while the other 295 (82.7%) had no restenosis. Lesion location, calcification degree, balloon expansion pressure, residual stenosis, intraprocedural dissection, and cerebral blood flow TICI grade were significant (P < 0.05) risk factors for in-stent restenosis. The in-stent restenosis prediction model was established as follows: P = 1/[1 + e-(-6.070-1.391 location + 2.745 calcification + 4.117 balloon inflation pressure + 2.195 intraprocedural dissection + 1.163 residual stenosis + 1.174 flow TC grade)]. In the validation group, the AUC in the ROC curve analysis was 0.902 (95% CI: 0.836-0.969), and when the cutoff value was 0.50, the sensitivity and specificity of this model were shown to be 76.92% and 80.26%, respectively, in predicting in-stent restenosis at angiographic follow-up, with a total coincidence rate of 79.78%. In conclusion, in-stent restenosis after intracranial Enterprise stenting is affected by stenosis location, calcification, balloon inflation pressure, intraprocedural arterial dissection, residual stenosis, and cerebral flow grade, and establishment of a logistic model with these factors can effectively predict in-stent restenosis.

Circ_DHRS3 positively regulates GREM1 expression by competitively targeting miR-183-5p to modulate IL-1ß-administered chondrocyte proliferation, apoptosis and ECM degradation.

BACKGROUND: Osteoarthritis (OA) is a chronic inflammatory disease caused by degenerative changes of articular cartilage, involving in the expression changes of special circular RNAs (circRNAs). This study aimed to explore the role of circ_DHRS3 in OA cell models and provide a potential mechanism. METHODS: OA cell models were constructed using human chondrocytes with Interleukin-1 beta (IL-1ß) treatment. The expression of circ_DHRS3, microRNA (miR)-183-5p and Gremlin 1 (GREM1) mRNA was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was identified using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis was investigated using flow cytometry assay. The protein levels of proliferation- and apoptosis-related proteins were quantified by western blot. The levels of extracellular matrix (ECM)-associated proteins were quantified by western blot to assess ECM degradation. The relationship between miR-183-5p and circ_DHRS3 or GREM1 was predicted and then verified by dual-luciferase reporter assay. RESULTS: Circ_DHRS3 expression was elevated in OA cartilage tissues and IL-1ß-treated chondrocytes. Circ_DHRS3 was resistant to RNase R and Actinomycin D. Circ_DHRS3 knockdown promoted chondrocyte proliferation inhibited by IL-1ß, and alleviated IL-1ß-induced apoptosis and ECM degradation, which were reversed by the inhibition of miR-183-5p, a target of circ_DHRS3. MiR-183-5p restoration also enhanced IL-1ß-blocked cell proliferation, and relieved IL-1ß-induced cell apoptosis and ECM degradation, while GREM1 (a target of miR-183-5p) overexpression abolished the effects of miR-183-5p restoration. Moreover, circ_DHRS3 regulated GREM1 expression by targeting miR-183-5p. CONCLUSION: Circ_DHRS3 mediated IL-1ß-administered chondrocyte proliferation, apoptosis and ECM degradation by positively regulating GREM1 expression via competitively targeting miR-183-5p.

Surface-agnostic highly stretchable and bendable conductive MXene multilayers.

Stretchable, bendable, and foldable conductive coatings are crucial for wearable electronics and biometric sensors. These coatings should maintain functionality while simultaneously interfacing with different types of surfaces undergoing mechanical deformation. MXene sheets as conductive two-dimensional nanomaterials are promising for this purpose, but it is still extremely difficult to form surface-agnostic MXene coatings that can withstand extreme mechanical deformation. We report on conductive and conformal MXene multilayer coatings that can undergo large-scale mechanical deformation while maintaining a conductivity as high as 2000 S/m. MXene multilayers are successfully deposited onto flexible polymer sheets, stretchable poly(dimethylsiloxane), nylon fiber, glass, and silicon. The coating shows a recoverable resistance response to bending (up to 2.5-mm bending radius) and stretching (up to 40% tensile strain), which was leveraged for detecting human motion and topographical scanning. We anticipate that this discovery will allow for the implementation of MXene-based coatings onto mechanically deformable objects.

Seasonal, Lunar and Tidal Influences on Habitat Use of Indo-Pacific Humpback Dolphins in Beibu Gulf, China.

Shanshan Li, Huili Gao, Xiuqing Hao, Lin Zhu, Ting Li, Hongke Zhang, Yi Zhou, Xinrong Xu, Guang Yang, and Bingyao Chen (2018) Cetacean habitat use based on different environmental phases varies between species and geographies, and little is known about Pacific humpback dolphin habitat use in the Beibu Gulf. Here we aimed to identify seasonal, lunar and tidal influences on the spatial use of Beibu humpback dolphins based on two parameters: water depth and distance to an estuary. The ANOVA test indicated that habitat use was influenced by seasons and tidal phases, but not lunar phases. The humpback dolphins utilized shallow areas near an estuary throughout the wet season and high tides, and moved toward deeper water during the dry season and low tides. This habitat preference is likely synchronized with prey seasonal and tidal movements. The wet season and high tides bring abundant prey resources and increase accessibility to inshore shallow waters for humpback dolphins. The present study provides new information on regular habitat use by Indo- Pacific humpback dolphins, which is crucial for developing effective conservation strategies.

Role of autophagy and mTOR signaling in neural differentiation of bone marrow mesenchymal stem cells.

Autophagy is involved in cell differentiation. We present evidence that autophagy is activated during ß-mercaptoethanol (ß-ME)-induced neuronal differentiation of bone marrow mesenchymal stem cells (MSCs), in which mammalian target of rapamycin (mTOR) signaling is important. mTOR activity declined after being transported from the nucleus to the cytoplasm. Using 3-methyladenine (3-MA) and rapamycin to regulate the activity of mTOR, it was found that the efficiency of neuronal differentiation was affected.

[A preliminary study of plasma microRNA levels in children with methylmalonic acidemia].

OBJECTIVE: To screen out differentially expressed microRNAs (miRNAs) in the plasma of children with methylmalonic acidemia (MMA), to determine the expression of miR-9-1 in plasma and to preliminarily evaluate the significance of miR-9-1 as a biomarker in MMA. METHODS: Plasma was obtained from 17 MMA children, 10 hyperhomocysteinemia (HHcy) children without MMA (HHcy group), and 10 normal controls. Of 17 MMA children, 12 had HHcy (MMA+HHcy group), and 5 had no HHcy (MMA group). The differentially expressed miRNAs were screened out by miRNA microarray. Differentially expressed miR-9-1 was selected, and plasma miR-9-1 levels were determined by RT-PCR. Urine was collected from MMA patients who received vitamin B12 treatment, and plasma miR-9-1 levels were determined by RT-PCR after treatment. RESULTS: The miRNA microarray analysis showed that 26 miRNAs were differentially expressed, among which 16 miRNAs (including miR-9-1) were down-regulated over 2 times, while 10 miRNAs were up-regulated over 2 times. The MMA+HHcy , MMA and HHcy groups had significantly down-regulated miR-9-1 compared with the normal control group (P<0.01). The patients who showed a good response to vitamin B12 treatment had significantly increased plasma miR-9-1 levels, without significant difference compared with the normal control group. CONCLUSIONS: Plasma miR-9-1 is significantly down-regulated in MMA patients, but it is significantly up-regulated after vitamin B12 treatment, suggesting that miR-9-1 may act as a biomarker in monitoring the progression of MMA.

MicroRNA-9 regulates neural apoptosis in methylmalonic acidemia via targeting BCL2L11.

Methylmalonic acidemia (MMA) is an autosomal-recessive inborn metabolic disorder that results from a deficiency in methylmalonyl-coenzyme A mutase or its cofactor, adenosylcobalamin. Currently, neurological manifestations in MMA are thought to be associated with neural apoptosis. BCL2L11, which is a proapoptotic Bcl-2 family member, is resident in the outer mitochondrial membrane, where this protein acts as a central regulator of the intrinsic apoptotic cascade and mediates excitotoxic apoptosis. MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Currently, little is known regarding the role of miRNA in MMA. In our previous study, we preliminarily found that the expression of miR-9 was significantly down-regulated in MMA patient plasma and sensitively changed after VitB12 treatment, which may act as a potential "competitor" of gas chromatography-mass spectrometry for the diagnosis of MMA. In the present study, we first confirmed that miR-9 inhibited BCL2L11 expression by directly targeting its 3'-untranslated region, and the up-regulation of miR-9 reduced neural apoptosis induced by methylmalonate via targeting BCL2L11. Taken together, our results suggested that miR-9 might act as a monitor of changes in MMA and might provide new insights into a therapeutic entry point for treating MMA.

A Primary Study on Down-Regulated miR-9-1 and Its Biological Significances in Methylmalonic Acidemia.

Methylmalonic acidemia (MMA) is a metabolic disorder, which is caused by a deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase. MMA diagnosis is dependent on the method of gas chromatography-mass spectrometry, which is expensive, complicated, and time consuming. Currently, microRNAs (miRNAs) have gained considerable interest for its function as a novel class of non-invasive and sensitive biomarkers for the diagnosis of diseases. However, there has been no related report regarding its role in MMA. Our study first detected differentially expressed microRNAs in MMA and found that the expression of miR-9-1 was significantly down-regulated and changed sensitively after VitB12 treatment. Furthermore, we confirmed that miR-9-1 was able to suppress neuronal apoptosis induced by methylmalonate. Taken together, our results suggested that miR-9-1 may act as a potential biomarker for the diagnosis and monitoring of changes in MMA and provide new insights into the pathogenesis of MMA.

Effect of Erzhi Pill (二至丸) on improving cerebral nerve cell apoptosis in aging rats.

OBJECTIVE: To investigate the effects of Erzhi Pill (二至丸,EZP) on nerve cell apoptosis in senescence model rats. METHODS: The rats model of senescence was established by peritoneal D-galactose injection combined with thymusectomy. Forty SD rats were randomized into four groups, the normal control group, the senescence model group, the EZP treated group, and the vitamins treated group, 10 in each group. The rats were made into senescence model except those in the normal group. In the same time of D-galactose injection, the rats were treated respectively with distilled water, EZP 4.32 g/kg, and vitamins E and C 0.06 g/kg daily for 6 weeks via intragastric infusion. The index of main viscera (as brain, testis, etc.), serum levels of superoxide dismutase (SOD) activity, and total anti-oxidation capacity (T-AOC) were measured after a 6-week treatment. Meanwhile, the cerebral cortex neuronal apoptosis proportion and mitochondrial membrane potential (MMP) were detected by flow cytometry. RESULTS: Both EZP and vitamins E and C treatments showed effects on increasing testis index and serum level of T-AOC, reducing the percentage of neuronal apoptosis in the cerebral cortex, and elevating MMP in the aging rats model. CONCLUSIONS: EZP could inhibit the cerebral cortex neuron apoptosis and maintain the mitochondrial function in the senescent process of rats induced by peritoneal D-galactose injection combined with thymusectomy. It also shows antioxidation effect to some extents.

[Study of molecular mechanism of anti-Parkinson's disease traditional Chinese medicine using model of Caenorhabditis elegans].

Parkinson's disease (PD) is a neurodegenerative disorder with a complex, multifactorial aetiology. The brains of patients affected with PD are characterized by a loss of neurons in dopamine neurons in the substantia nigra, decreasing of dopamine secretion, and the deposition of Lewy bodies (LBs) in the cytoplasm of remaining neurons. In China the data show that the incidence of Parkinson's disease increases at least 20 times in recent 20 years, and it makes things worse for the aging society. Developing good anti-PD drugs to improve the patient's quality of life is particularly important. The treatment of PD using traditional Chinese medicine (TCM) has made remarkable effect, while the the molecular mechanisms of it is still not known, while elucidating the molecular mechanism of TCM is the base of better understanding its function. Using genetically modified PD model of Caenorhabditis elegans, which is suitable for molecular mechanism study, to explore the interference mechanism of TCM to PD might be an effective way. This review briefly introduces the research progress on molecular mechanism of PD, and then discusses the idea of using C. elegans to study molecular mechanism of TCM intervention to PD.

[Research progress on mechanism of delaying senility of Chinese materia medica in recent years].

Recently investigating mechanisms on delaying aging of traditional Chinese medicine (TCM) and discovering high effective related medicines have been become hot spot and have achieved some progress. This review comprehensively analyzed the mechanism of TCM on delaying senility in recent years. The modern researches have demonstrated that Chinese materia medica and compound formulas can retard aging process by anti-oxidant activity of free radical, modulating metabolism of neuroendocrine, balancing immunological function, prolonging telomere length and promoting telomerase activity in cells, anti-DNA damage of cells, and controlling expression of gene and protein involved in cell proliferation.