Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampu

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Hemispheric dispersion of radioactive plume laced with fission nuclides from the Fukushima nuclear event

Radioactivities of particulate 131I and 137Cs released from the Fukushima nuclear accident were monitored in a regional aerosol network including two high mountain sites (central Taiwan and Tibetan Plateau). The results were integrated with data measured elsewhere around the world, with special focus on the mid-latitudes. The hemispheric transport of the Fukushima radiation clouds (FRCs) by the westerlies took $18 days, displaying an exponential-like decrease eastward, with a dilution factor of at least five orders of magnitude following a full circuit around the globe. The initial two waves of FRCs may travel at different atitudes: the first one at$3–4 km, whereas the second one up to 5 km or more. 131I and 137Cs were fractionated during transport, with 137Cs concentrated in the shallower layer, susceptible to depositional removal, while 131I moving faster and higher. This accident may be exemplified to identify some atmospheric processes on the hemispheric scale

Extending the Pre-Training of BLOOM for Improved Support of Traditional Chinese: Models, Methods and Results

In this paper we present the multilingual language model BLOOM-zh that features enhanced support for Traditional Chinese. BLOOM-zh has its origins in the open-source BLOOM models presented by BigScience in 2022. Starting from released models, we extended the pre-training of BLOOM by additional 7.4 billion tokens in Traditional Chinese and English covering a variety of domains such as news articles, books, encyclopedias, educational materials as well as spoken language. In order to show the properties of BLOOM-zh, both existing and newly created benchmark scenarios are used for evaluating the performance. BLOOM-zh outperforms its predecessor on most Traditional Chinese benchmarks while maintaining its English capability. We release all our models to the research community

EFFECT OF ORAL ADMINISTRATION OF PHERETIMA ASPERGILLUM (EARTHWORM) IN RATS WITH CEREBRAL INFARCTION INDUCED BY MIDDLE-CEREBRAL ARTERY OCCLUSION.

We investigated the curative effect of Pheretima aspergillum (earthworm, PA) on rats with middle cerebral artery occlusion (MCAo). The MCAo-induced cerebral infarction was established and its underlying mechanisms by counting the infarction areas and evaluating the rats’ neurological status. Immunostaining was used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B, and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that oral administration of PA for two weeks to rats with MCAo successfully reduced cerebral infarction areas in the cortex and striatum, and also reduced scores of neurological deficit. The PA-treated MCAo rats showed greatly decreased neuronal death, glial proliferation, and S100B proteins in the penumbra area of the cortex and in the ischemic core area of the cortex, but BDNF did not changed. These results demonstrated novel and detailed cellular mechanisms underlying the neuroprotective effects of PA in MCAo rats

Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is composed of cardiovascular risk factors including insulin resistance, obesity, dyslipidemia, and hypertension. Most of the components of MetS have been linked to the development of neoplasm. The purpose of this study was to evaluate the relationship between individual components of MetS and colorectal adenoma.</p> <p>Methods</p> <p>The study subjects were recruited from a pool of 4872 individuals who underwent a health check-up examination during the period January 2006 to May 2008. Each participant fulfilled a structured questionnaire. MetS was defined based on the America Heart Association and National Heart Lung Blood Institute criteria. Subjects with history of colon cancer, colon polyps, colitis, or prior colonic surgery were excluded.</p> <p>Results</p> <p>A total of 4122 subjects were included for final analysis (2367 men and 1755 women; mean age, 49.6 ± 11.7 years). Of them, MetS was diagnosed in 708 men (29.9%) and in 367 women (20.9%). Among the patients with MetS, 34.6% had adenoma, 31.7% had hyperplastic polyps and 23.3% were polyp-free (p < 0.0001, Chi-square test). The adjusted OR for colorectal adenoma was significantly higher in the subjects with MetS (OR, 1.31, CI: 1.09-1.57). A stronger association between MetS and colorectal adenoma was found in men (OR:1.44, CI:1.16-1.80) than in women (OR:1.04, CI:0.74-1.46). The adjusted OR for adenoma increased as the number of MetS components increased (p for trend = 0.0001 ). When the individual components of MetS were analyzed separately, only central obesity (OR:1.36, CI:1.14-1.63), low HDL cholesterol levels (OR:1.30, CI:1.10-1.54) and high triglyceride levels (OR:1.26, CI:1.04-1.53) were independently associated with colorectal adenoma.</p> <p>Conclusions</p> <p>Of the components of MetS analyzed in this study, central obesity and dyslipidemia are independent risk factors for colorectal adenoma. With regard to the prevention of colorectal neoplasm, life-style modification such as weight reduction is worthwhile.</p

Albuminâ bilirubin gradeâ based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma

Background & AimsThe prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albuminâ bilirubin (ALBI) gradeâ based nomogram of BCLC to estimate survival for individual HCC patient.MethodsBetween 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram.ResultsBeta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3â and 5â year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71â 0.81) in the derivation cohort and 0.76 (95% CI: 0.71â 0.81) in the validation cohort. The calibration plots to predict both 3â and 5â year survival rate well matched with the 45â degree ideal line for both cohorts, except for ALBIâ based BCLC stage 0 in the validation cohort.ConclusionsThe proposed ALBIâ based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and userâ friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/1/liv14249_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/2/liv14249.pd

Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized