Patient with multiple morphological abnormalities of sperm flagella caused by a novel ARMC2 mutation has a favorable pregnancy outcome from intracytoplasmic sperm injection.

PURPOSE: To investigate the potential genetic cause in a primary infertility patient with multiple morphological abnormalities of sperm flagella (MMAF). METHODS: The patient's sperm was observed by light and electron microscopy. Whole-exome sequencing (WES) was carried out to identify candidate genes. Then, the mutation found by WES was verified by Sanger sequencing. The proteins interacting with ARMC2 were revealed by co-immunoprecipitation (co-IP) and mass spectrometry. Intracytoplasmic sperm injection (ICSI) was carried out to achieve successful pregnancy. RESULTS: Typical MMAF phenotype (absent, short, coiled, bent irregular flagella) was shown in the patient's sperm. A novel homozygous mutation in ARMC2 (c.1264C > T) was identified. The proteins interacting with ARMC2 we found were CEP78, PGAM5, RHOA, FXR1, and SKIV2L2. The ICSI therapy was successful, and boy-girl twins were given birth. CONCLUSION: We found a novel mutation in ARMC2 which led to MMAF and male infertility. This is the first report of ICSI outcome of patient harboring ARMC2 mutation. The interacting proteins indicated that ARMC2 might be involved in multiple processes of spermatogenesis.

Cryptotanshinone inhibits RANKL-induced osteoclastogenesis by regulating ERK and NF-κB signaling pathways.

Osteoporosis (OS) is one of the most common healthy problems characterized by low bone mass. Osteoclast, the primary bone-resorbing cell, is responsible for destructive bone diseases including osteoporosis (OS). Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza bunge, has been shown to prevent the destruction of cartilage and the thickening of subchondral bone in mice osteoarthritis models. However, its molecular mechanism in osteoclastogenesis needs to be determined. The aim of the current study was to explore the effect of CTS on osteoclastogenesis and further evaluate the underlying mechanism. Our results showed that CTS inhibited receptor activator of NF-κB ligand (RANKL)-induced the increase in tartrate-resistant acid phosphatase (TRAP) activity in bone marrow-derived macrophages (BMMs). In addition, the expressions of osteoclastogenesis-related marker proteins and nuclear factor of activated T-cells (NFAT) activation were suppressed by CTS treatment in BMMs. Furthermore, CTS attenuated RANKL-induced ERK phosphorylation and NF-κB activation in BMMs. These findings indicated that CTS inhibited RANKL-induced osteoclastogenesis by inhibiting ERK phosphorylation and NF-κB activation in BMMs. Thus, CTS may function as an inhibitor of osteoclastogenesis and may be considered as an alternative medicine for the prevention and treatment of OS.

Down-regulation of miR-193a-3p promotes osteoblast differentiation through up-regulation of LGR4/ATF4 signaling.

Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR-193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling.

Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations.

Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development.

Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic osteochondropathy. In this study, we conducted the first genome-wide copy number variation study (GCNVS) of KBD totally involving 2,743 Chinese Han adults. GCNVS was first performed using Affymetrix Human SNP6.0 Arrays. The identified copy number variations (CNVs) were then replicated in an independent Chinese Han sample containing 1,026 subjects. SNP genotyping, CNV identification and quality control were implemented by Birdsuite. STRUCTURE and EIGENSTRAT were applied for controlling potential population stratification in the GCNVS. Association analysis was conducted using PLINK. Microarray and qRT-PCR were also conducted to compare the expression levels of the genes overlapping with identified CNVs between KBD patients and healthy controls. GCNVS found that CNV452 (P value = 7.78 × 10(-5)) overlapping with ABI3BP gene was significantly associated with KBD. Replication association study observed that rs9850273 (P value = 0.008) and rs7613610 (P value = 0.021) in ABI3BP gene were significantly associated with KBD. Gene expression analysis also found that ABI3BP was up-regulated in KBD patients compared to healthy controls. Our results suggest that ABI3BP was a novel susceptibility gene for KBD.

[Functional connectivity in ischemia stroke motor aphasia patients during resting state].

OBJECTIVE: To investigate the changes of Broca's area functional connectivity in ischemia stroke patients with motor aphasia during resting state using functional magnetic resonance imaging (fMRI). METHODS: The functional connectivity of Broca's area was analyzed by observing the correlation between low frequency signal fluctuations in Broca's area and those in all brain regions. RESULTS: In the normal controls group, there was multiple brain area positively correlated with Broca's area during resting state. The patients group compared with controls group, the functional connectivity between Broca's area and adjacent brain regions around its is most significant, and its controlateral brain area correlated with Broca's area reduced, but some cerebellum, occipital lobe, middle temporal gyrus and corpus callosum spenium correlated with Broca's area strengthened. CONCLUSION: There is a wide range of motor function of language network during resting state. The right anterior cingulate gyrus, knee of corpus callosum and hemisphere play an important part in motor language function network. The enhancement functional connectivity between the adjacent brain regions surrounding Broca's area, the right cerebellum, occipital lobe, middle temporal gyrus and spenium of corpus callosum and Broca's area may be one compensatory mechanism remodeling for the language recover of ischemia stroke patients with motor aphasia.

Identification of macrophage-related genes in bladder cancer patients using single-cell sequencing and construction of a prognostic model.

Single-cell sequencing is an emerging technology that can effectively identify cell types in tumors. In the tumor microenvironment of bladder cancer, macrophages play a crucial role in invasion and immune escape. This study aimed to assess the expression of macrophage-related genes (MRGs) in the tumor microenvironment of bladder cancer patients and construct a prognostic model based on MRGs using bioinformatics methods. METHODS: Single-cell sequencing data from bladder cancer patients was downloaded from the GEO. After quality control and cell type identification, macrophages in the samples were extracted for re-clustering. Feature genes were then identified, and MRGs were assessed. Genetic data from TCGA database bladder cancer patients was also downloaded and organized. The intersection of MRGs and the TCGA gene set was determined. Clinical information was connected with this intersection, and the data was divided into training and validation sets. The training set was used for model construction and the validation set for model verification. A prognostic model based on MRGs was built using the LASSO algorithm and Cox regression. Patients were divided into high-risk and low-risk groups based on their prognostic features, and survival information in the training and validation sets was observed. The predictive ability of the model was assessed using a ROC curve, followed by a calibration plot to predict 1-, 3-, and 5-year survival rates. RESULTS: Four cell types were identified, and after extracting macrophages, three cell subgroups were clustered, resulting in 1,078 feature genes. The top 100 feature genes from each macrophage subgroup were extracted and intersected with TCGA expressed genes to construct the model. A risk prediction model composed of CD74, METRN, PTPRR, and CDC42EP5 was obtained. The survival and ROC curves showed that this model had good predictive ability. A calibration curve also demonstrated good prognostic ability for patients. CONCLUSION: This study, based on single-cell data, TCGA data, and clinical information, constructed an MRG-based prognostic model for bladder cancer using multi-omics methods. This model has good accuracy and reliability in predicting the survival and prognosis of patients with bladder cancer, providing a reference for understanding the interaction between MRGs and bladder cancer.

Genome-wide study identifies the regulatory gene networks and signaling pathways from chondrocyte and peripheral blood monocyte of Kashin-Beck disease.

This investigation was designed to unravel gene networks in Kashin-Beck disease (KBD) and better identify target genes of KBD for gene therapy development. RNA was isolated separately from cartilage and peripheral blood samples of patients with KBD and healthy controls. Agilent 44K human whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. Three significant canonical pathways and nine chondrocyte networks from chondrocytic gene expression profiles were screened using ingenuity pathway analysis (IPA), but only one network and no canonical pathways from peripheral blood monocytic gene profile were identified. Bak1, APAF-1, CASP6, IGFBP2, Col5a2 and TGFBI extracted from significant genes that involved in chondrocytic canonical pathways and networks may have closer relationship with the etiopathogenesis of KBD. Those genes may be potential targets for gene diagnosis and treatment. Six physiological functions were predominant and unique to the chondrocytic genes, whereas two were unique to peripheral blood monocytic genes. The identified genes may represent a source of potentially novel molecular targets, which may provide a better understanding of the molecular details in KBD pathogenesis and also provide useful pathways and network maps for the future research in osteochondrosis.

The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease.

BACKGROUND: The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD). METHODS: The changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients. RESULTS: It was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 µM. CONCLUSION: These findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.

Trajectory and Sway Prediction Towards Fall Prevention.

Falls are the leading cause of fatal and non-fatal injuries, particularly for older persons. Imbalance can result from the body's internal causes (illness), or external causes (active or passive perturbation). Active perturbation results from applying an external force to a person, while passive perturbation results from human motion interacting with a static obstacle. This work proposes a metric that allows for the monitoring of the persons torso and its correlation to active and passive perturbations. We show that large changes in the torso sway can be strongly correlated to active perturbations. We also show that we can reasonably predict the future path and expected change in torso sway by conditioning the expected path and torso sway on the past trajectory, torso motion, and the surrounding scene. This could have direct future applications to fall prevention. Results demonstrate that the torso sway is strongly correlated with perturbations. And our model is able to make use of the visual cues presented in the panorama and condition the prediction accordingly.

Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model.

Purpose: Dry eye disease (DED) is a multifactorial disease that is associated with inflammation. Excessive DNA is present in the tear fluid of patients with DED. Absent in melanoma 2 (AIM2) is a key DNA sensor. This study aimed to investigate the role of AIM2 in the pathogenesis of DED. Methods: DED was induced by injection of scopolamine (SCOP). Aberrant DNA was detected by cell-free DNA (cfDNA) ELISA and immunostaining. Corneal epithelial defects were assessed by corneal fluorescein staining, zonula occludens-1 immunostaining and TUNEL. Tear production was analyzed by phenol red thread test. Lacrimal gland (LG) histology was evaluated by hematoxylin and eosin staining, and transmission electron microscopy examination. Macrophage infiltration in LG was detected by immunohistochemistry for the macrophage marker F4/80. Gene expression was analyzed by RT-qPCR. Protein production was examined by immunoblot analysis or ELISA. Results: Aim2-/- mice displayed a normal structure and function of LG and cornea under normal conditions. In SCOP-induced DED, wild type (WT) mice showed increased cfDNA in tear fluid, and aberrant accumulations of dsDNA accompanied by increased AIM2 expression in the LG. In SCOP-induced DED, WT mice displayed damaged structures of LG, reduced tear production, and severe corneal epithelium defects, whereas Aim2-/- mice had a better preserved LG structure, less decreased tear production, and improved clinical signs of dry eye. Furthermore, genetic deletion of Aim2 suppressed the increased infiltration of macrophages and inhibited N-GSDMD and IL18 production in the LG of SCOP-induced DED. Conclusions: Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.

Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation.

Hedgehog (Hh) signaling is well known for its crucial role during development, but its specific role in individual cell lineages is less well characterized. Here, we disrupted Hh signaling specifically in melanocytes by using Cre-mediated cell-type-specific knockout of the Hh regulator suppressor of fused (Sufu). Interestingly, corresponding mice were fully pigmented and showed no developmental alterations in melanocyte numbers or distribution in skin and hair follicles. However, there were ectopic melanoblasts visible in the anterior chamber of the eye that eventually displayed severe malformation. Choroidal melanocytes remained unaltered. Surprisingly, the abnormal accumulation of anterior uveal melanoblasts was not the result of increased cell proliferation but of increased migration to ectopic locations such as the cornea. In melanoblasts in vitro, Sufu knockdown replicated the increase in cell migration without affecting proliferation and was mediated by an increased level of phosphorylated-ERK brought about by a reduction in the levels of the repressor form of GLI3. These results highlight the developmental divergence of distinct melanocyte subpopulations and may shed light on the pathogenesis of human ocular melanocytosis.

A novel signature constructed by differential genes of muscle-invasive and non-muscle-invasive bladder cancer for the prediction of prognosis in bladder cancer.

Background: Bladder cancer (BCa) is a malignant tumor that usually forms cancer cells in the inner lining of the bladder. Hundreds of thousands of people worldwide have BCa diagnosed each year. The purpose of this study was to construct a prognostic model by differential expression of genes between muscular and non-muscular invasive BCa, and to investigate the prognosis of BCa patients. Methods: The data of BCa patients was sourced from the GEO and TCGA database. Single-cell sequencing data was obtained from three patients in the GSE135337 database, and microarray data for verification was obtained from GSE32894. Univariate, Lasso and multivariate cox regression analyses were performed to construct the prognostic model. The prognostic features, immune features and drug sensitivity of the model were further evaluated. Single-cell data and microarray data were used to validate the differential expression of model genes between muscle-invasive and non-muscle-invasive BCa. The invasion and migration of BCa cells were evaluated using the transwell assay and wound-healing assay. The cell proliferation capacity was simultaneously evaluated using Colony formation experiments. The protein expression of the specific gene was detected by western blot analysis. Results: We identified 183 differentially expressed muscle-invasive-related differential genes (MIRDGs), among which four were selected to establish a prognostic model. Based on our signature, patients in different groups displayed varying levels of immune infiltration and immunotherapy profiles. Single-cell sequencing data and microarray data confirmed that four invasion-related genes were expressed at higher levels in muscle-invasive BCa. Given the critical role of S100A9 in the progression of BCa, we performed further analysis. The results showed that protein expression of S100A9 was high in muscle-invasive BCa, and S100A9 knockdown could inhibit the proliferation, migration and invasion of BCa. Conclusion: These findings demonstrated that the prognostic model for BCa patients was reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of BCa patients in the future. S100A9 may become a better prognostic marker and potential therapeutic target to further guide clinical treatment decisions.

Expression profile analysis of mycotoxin-related genes in cartilage with endemic osteochondropathy Kashin-Beck Disease.

BACKGROUND: Kashin-Beck Disease (KBD) is an endemic osteochondropathy. Mycotoxins are believed to play an important role in the pathogenesis of KBD. Because the molecular mechanism of mycotoxin-induced cartilage lesions remains unclear, there is not effective treatment for KBD now. To identify key genes involved in the mycotoxin-induced cartilage lesions, we compared the expression profiles of mycotoxin-related genes (MRG) between KBD cartilage and healthy cartilage. METHODS: Total RNA was isolated from cartilage samples, following by being amplified, labeled and hybridized to Agilent human whole genome microarray chip. qRT-PCR was conducted to validate the microarray data. 1,167 MRG were derived from the environmentally related genomic database Toxicogenomics. The microarray data of MRG was subjected to single gene and gene ontology (GO) expression analysis for identifying differently expressed genes and GO. RESULTS: We identified 7 up-regulated MRG and 2 down-regulated MRG in KBD cartilage, involved in collagen, apoptosis, metabolism and growth & development. GO expression analysis found that 4 apoptosis-related GO and 5 growth & development-related GO were significantly up-regulated in KBD cartilage. CONCLUSIONS: Based on the results of previous and our studies, we suggest that mycotoxins might contribute to the development of KBD through dysfunction of MRG involved in collagen, apoptosis and growth & development in cartilage.

[Study of functional magnetic resonance imaging repeatability of linguistic-functional cortex].

OBJECTIVE: To explore the reproducibility and stability of brain functional area in the response of language tasks during Chinese word processing with functional magnetic resonance imaging (fMRI) by follow-up scanning so as to provide rationales for clinical preoperative localization and the mechanisms of recovery from aphasia. METHODS: The fMRI data were collected by scanning semantic and phonologic judgments in 15 healthy volunteers. Each subject was scanned twice by the same fMRI procedure of both language tasks with an interval of 1 month. By analyzing the effective overlapping average activation maps, the reproducibility of inter-subject imaging result for two language tasks were estimated by selecting the main language areas, such as Broca's area and Wernicke's area as the region of interest (ROI). By individually calculating the spatial distance of ROI centroid coordinates in the same activating range before and after test, the inter-subject stability in between-session was calculated quantitatively. RESULTS: Both language tasks activated more than one language-related brain areas in cerebral hemispheres. Both language tasks induced significant BOLD response in Broca's and Wernicke's areas with a tendency of left lateralization. The number of subjects in terms of the activation of both language tasks in Broca's and Wernicke's areas accounted over a half of the total subjects. As compared with the phonologic judgment task, the semantic judgment task showed better reproducibility in Broca's area. In the same spatial distance of ROI centroid coordinates, the stability of Broca's area was higher than that of Wernicke's area while the stability of semantic judgment in Broca's area higher than that of phonologic judgment. CONCLUSION: Such main language domains as Broca's and Wernicke's areas can be effectively activated by both semantic and phonologic judgments. By comparison, semantic judgment in Broca's area shows a higher level of reproducibility and stability. Thus it is applicable for clinical preoperative localization and the mechanisms of recovery from aphasia.

Phosphorus removal from wastewater using electric arc furnace slag aggregate.

Electric arc furnace (EAF) slag aggregate, a waste by-product of the steel industry, exhibited a high potential for phosphorus (P) removal and had attracted considerable attention. The main objectives of this study were to evaluate the performance of using EAF slag aggregate as an adsorbent for P removal and identify its P removal capacity. A series of batch tests showed that P removal capacity of EAF slag increases gradually with the increase of pH with a range of 2-10, while the highest P removal capacity (1.94 mg/g) can be obtained at pH 12. The adsorption kinetics of P on EAF slag can be described by pseudo-second-order kinetic equations. Isothermal adsorption simulations showed that the best fitted model was the Freundlich model with a correlation coefficient of 0.9825. A continuous flow column experiment feeding a synthetic influent containing 15 mg P/L was operated for 60 days and the P removal efficiency was greater than 95% with a P removal capacity of 1.6 mg P/g slag. The results obtained in this study showed that EAF slag could act as an efficient adsorbent for P removal. Calcium phosphate precipitation depends on the release of Ca2+ and OH- by the dissolution of calcium oxide in EAF slag was found to be the dominant removal mechanism for P removal.

Applications of Sponge Iron and Effects of Organic Carbon Source on Sulfate-Reducing Ammonium Oxidation Process.

The typical characteristics of wastewater produced from seafood, chemical, textile, and paper industries are that it contains ammonia, sulfate, and a certain amount of chemical oxygen demand (COD). The sulfate-reducing ammonium oxidation process is a biochemical reaction that allows both ammonia and sulfate removal, but its low growth rate and harsh reaction conditions limit its practical application. Due to the adsorption properties of the iron sponge and its robust structure, it provides a suitable living environment for microorganisms. To reduce the negative impact on the environment, we employed 4.8 kg of sponge iron in a 2.0 dm3 anaerobic sequencing batch reactor (ASBR). We investigated the effects of the type and concentration of carbon sources on the performance of the sulfate-reducing ammonium oxidation (SRAO) process. The results demonstrated that during a start-up period of 90 days, the average ammonium removal efficiency and the sulfate conversion efficiency of the reactor containing the sponge iron were 4.42% and 8.37% higher than those of the reactor without the sponge iron. The addition of the sponge iron shortens the start-up time of this greenhouse gas-free denitrification process and reduces future costs in practical applications. The removal of total nitrogen (TN) significantly increased after adding organic carbon sources and then declined sharply, while the most considerable reduction of ammonium removal efficiency from 98.4% to 30.5% was observed with adding phenol. The performance of the group employing glucose as the carbon source was recovered on the 28th day, with the average ammonium removal efficiency increasing from 49.03% to 83.5%. The results of this simulation study will help the rapid start-up of SRAO in the water treatment industry and can precisely guide the application of the SRAO process for wastewater containing different organic carbon sources.

Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature.

Sperm carries male genetic information, and flagella help move the sperm to reach oocytes. When the ultrastructure of the flagella is abnormal, the sperm is unable to reach the oocyte and achieve insemination. Multiple morphological abnormalities of sperm flagella (MMAF) is a relatively rare idiopathic condition that is mainly characterized by multiple defects in sperm flagella. In the last decade, with the development of high-throughput DNA sequencing approaches, many genes have been revealed to be related to MMAF. However, the differences in sperm phenotypes and reproductive outcomes in many cases are attributed to different pathogenic genes or different pathogenic mutations in the same gene. Here, we will review information about the various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology (ART) outcomes. We will share our clinical detection and diagnosis experience to provide additional clinical views and broaden the understanding of this disease.

The change of the spinal cord ischemia-reperfusion injury in mitochondrial passway and the effect of the Ginkgo biloba extract's preconditioning intervention.

In order to explore whether the apoptosis in ischemia-reperfusion injury could be affected by Ginkgo biloba extract (GBE) and the free radical scavenger GBE could suppress this affection. Rabbits were randomly divided into sham group, ischemia group, ischemia-reperfusion group (1, 6, 24, 48 h), the drug group (1, 6, 24, 48 h). Measure the rate of apoptosis by flow cytometry, the caspase 9 and apoptosis-inducing factor (AIF) in the cytoplasm and serum by ELISA. Compared with the sham group and ischemia group, the reperfusion group increased the rate of apoptosis, the caspase 9 and AIF in serum have a peak at 24 h after reperfusion, in the cytoplasm the peak at 6 h.GBE inhibit performance has the systemic and local aspects. The apoptosis of nerve cells after spinal cord ischemia-reperfusion has the relationship with the mitochondrial caspase-dependent and caspase-independent pathways and both the local and systemic role. GBE inhibits nerve cell apoptosis by these ways.

Molecular mechanisms of cancer cachexia­induced muscle atrophy (Review).

Muscle atrophy is a severe clinical problem involving the loss of muscle mass and strength that frequently accompanies the development of numerous types of cancer, including pancreatic, lung and gastric cancers. Cancer cachexia is a multifactorial syndrome characterized by a continuous decline in skeletal muscle mass that cannot be reversed by conventional nutritional therapy. The pathophysiological characteristic of cancer cachexia is a negative protein and energy balance caused by a combination of factors, including reduced food intake and metabolic abnormalities. Numerous necessary cellular processes are disrupted by the presence of abnormal metabolites, which mediate several intracellular signaling pathways and result in the net loss of cytoplasm and organelles in atrophic skeletal muscle during various states of cancer cachexia. Currently, the clinical morbidity and mortality rates of patients with cancer cachexia are high. Once a patient enters the cachexia phase, the consequences are difficult to reverse and the treatment methods for cancer cachexia are very limited. The present review aimed to summarize the recent discoveries regarding the pathogenesis of cancer cachexia­induced muscle atrophy and provided novel ideas for the comprehensive treatment to improve the prognosis of affected patients.