Epidemiology of Sports-Related Sudden Death in Guangdong Province.

OBJECTIVES: By retrospective study of the epidemiological characteristics of sports-related sudden death (SrSD), the risk factors associated with SrSD were analyzed and explored to provide a scientific basis for comprehensive prevention and treatment of SrSD. METHODS: The personal information (sex, age, occupation, etc.), case information (time, place, type of sports, relative time between SrSD occurrence and exercise, etc.), death related information (sign or prodrome, medical history and surgical history, etc.), rescue situation (witnesses, on-site assistance, the availability of paramedics, etc.) of 374 SrSD cases in Guangdong Province from 2017 to 2021 were collected. Statistical analysis was conducted aiming at the key factors. RESULTS: In the 374 cases, there were significantly more males than females (19.78:1); the number of people aged between >39 and 59 was the largest (151, 40.37%); non-manual workers (68.98%) were more than manual workers; the top three sports with the highest number cases were basketball (34.49%), running (19.52%) and badminton (12.03%); from 3 pm to 9 pm (63.10%) was the time period with the highest incidence of events; sudden death mainly occurred during exercise (75.27%) and within 1 h after exercise (20.05%); the on-site rescue rate was very low (6.15%); the rate of autopsies was extremely low (1.07%); sudden cardiac death was the most common cause (67.11%). CONCLUSIONS: SrSD is most common in males aged >39 to 59 years old, mostly in non-manual workers, and usually occurs in basketball and running. Sudden death is more likely to occur during exercise and within 1 h after exercise. Therefore, the above potential risk factors should be focused on and studied in daily comprehensive prevention and treatment to provide scientific basis for accurate prevention and first aid of such sudden death.

Evaluation of Inspection Efficiency of Diatom Artificial Intelligence Search System Based on Scanning Electron Microscope.

OBJECTIVES: To explore the application values of diatom artificial intelligence (AI) search system in the diagnosis of drowning. METHODS: The liver and kidney tissues of 12 drowned corpses were taken and were performed with the diatom test, the view images were obtained by scanning electron microscopy (SEM). Diatom detection and forensic expert manual identification were carried out under the thresholds of 0.5, 0.7 and 0.9 of the diatom AI search system, respectively. Diatom recall rate, precision rate and image exclusion rate were used to detect and compare the efficiency of diatom AI search system. RESULTS: There was no statistical difference between the number of diatoms detected in the target marked by the diatom AI search system and the number of diatoms identified manually (P>0.05); the recall rates of the diatom AI search system were statistically different under different thresholds (P<0.05); the precision rates of the diatom AI system were statistically different under different thresholds(P<0.05), and the highest precision rate was 53.15%; the image exclusion rates of the diatom AI search system were statistically different under different thresholds (P<0.05), and the highest image exclusion rate was 99.72%. For the same sample, the time taken by the diatom AI search system to identify diatoms was only 1/7 of that of manual identification. CONCLUSIONS: Diatom AI search system has a good application prospect in drowning cases. Its automatic diatom search ability is equal to that of experienced forensic experts, and it can greatly reduce the workload of manual observation of images.

Assisting Role of Pulmonary Hypostasis Phenomenon in Diagnosis of Drowning.

OBJECTIVES: To study the phenomenon of pulmonary hypostasis in corpses of various causes of death, and to explore the potential value of this phenomenon in assisting forensic pathological diagnosis of drowning. METHODS: A total of 235 cases with clear cause of death through systematic autopsy were collected from January 2011 to June 2021 in Guangzhou. According to the location of body discovery, the cases were divided into the water body group (97 cases) and the non-water body group (138 cases), and the water body group was further divided into the water drowning group (90 cases) and the water non-drowning group (7 cases). Non-water body group was further divided into the non-water drowning group (1 case) and the non-water non-drowning group (137 cases). Three senior forensic pathologists independently reviewed autopsy photos to determine whether there was hypostasis in the lungs. The detection rate of pulmonary hypostasis was calculated. RESULTS: The detection rate of pulmonary hypostasis in the water drowning group (90 cases) was 0, and the negative rate was 100%. The detection rate of pulmonary hypostasis in the water non-drowning group (7 cases) was 100% and the negative rate was 0. The detection rate of pulmonary hypostasis in the water body group and in the non-water body group (after excluding 2 cases, 136 cases were calculated) was 7.22% and 87.50%, respectively. There were statistically significant differences in the detection rate of pulmonary hypostasis between water body group and non-water body group, and between water drowning group and water non-drowning group (P<0.05). CONCLUSIONS: The disappearance of pulmonary hypostasis can be used as a specific cadaveric sign to assist in the forensic pathological diagnosis of drowning.

Research Progress on Sport-Related Sudden Cardiac Death.

Physical exercise can reduce the overall risk of cardiovascular disease, prolong lifespan and improve the quality of life, but some studies have shown that there is a certain correlation between vigorous physical exercise and sudden cardiac death. A number of retrospective or prospective studies on sports-related sudden cardiac death (SrSCD) have been conducted at home and abroad. This article reviews the related studies on the definition, epidemiological characteristics, common causes of SrSCD and effects of excercise on cardiovascular function, pre-exercise screening and evaluation of SrSCD, in order to understand the latest research progress on SrSCD and provide clues and references for SrSCD research.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases.

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Teaching forensic pathology to undergraduates at Zhongshan School of Medicine.

Producing qualified forensic pathological practitioners is a common difficulty around the world. In China, forensic pathology is one of the required major subspecialties for undergraduates majoring in forensic medicine, in contrast to forensic education in Western countries where forensic pathology is often optional. The enduring predicament is that the professional qualities and abilities of forensic students from different institutions vary due to the lack of an efficient forensic pedagogical model. The purpose of this article is to describe the new pedagogical model of forensic pathology at Zhongshan School of Medicine, Sun Yat-sen University, which is characterised by: (a) imparting a broad view of forensic pathology and basic knowledge of duties and tasks in future careers to students; (b) educating students in primary skills on legal and medical issues, as well as advanced forensic pathological techniques; (c) providing students with resources to broaden their professional minds, and opportunities to improve their professional qualities and abilities; and (d) mentoring students on occupational preparation and further forensic education. In the past few years, this model has resulted in numerous notable forensic students accomplishing achievements in forensic practice and forensic scientific research. We therefore expect this pedagogical model to establish the foundation for forensic pathological education and other subspecialties of forensic medicine in China and abroad.

LNK deficiency aggravates palmitate-induced preadipocyte apoptosis.

LNK (SH2B3) is an intracellular adaptor protein that negatively regulates cellular proliferation or self-renewal of hematopoietic stem cells and some other progenitor cells. LNK is also recognized as a key regulator of insulin resistance and inflammatory responses in several tissues and organs. The function of LNK in adipose tissue is unknown. We previously demonstrated that type 2 diabetes mellitus (T2DM) mouse model had elevated serum free fatty acids (FFAs) levels and increased preadipocyte apoptosis in visceral fat tissue, showing the occurrence of lipotoxicity. Herein, when compared to control mice, the protein expression of LNK decreased in epididymal fat tissue from the high-sucrose/fat diet, low-dose streptozotocin induced T2DM mouse model. We thus investigated whether LNK could regulate palmitate-induced preadipocyte apoptosis in an in vitro apoptotic model in 3T3-L1 preadipocytes. LNK specific siRNA exacerbated palmitate-induced apoptosis and increased pro-apoptotic protein levels of cleaved caspase-3, Bax and cytochrome C; while overexpression of LNK cDNA exhibited significant anti-apoptotic effects. Consistently, LNK specific siRNA further decreased the Akt Ser-473 phosphorylation reduced by palmitate and located on upstream of Bax and cytochrome C. The siRNA-mediated LNK knockdown exacerbated mitochondrial membrane depolarization and mitochondrial-derived reactive oxygen species production induced by palmitate, whereas overexpression of LNK attenuated that. These results indicated that LNK plays a regulatory role in the palmitate-related preadipocyte apoptosis and might be involved in adipose tissue dysfunction.

Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway.

Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. We previously demonstrated that pretreatment with Xyl-B exerted neuroprotective effects and attenuated hypoxic-ischemic brain injury in neonatal mice. In the present study we investigated the neuroprotective effects of pre- and post-treatment with Xyl-B in adult mice using a transient middle cerebral artery occlusion (tMCAO) model, and explored the underlying mechanisms. Adult male C57 mice were subjected to tMCAO surgery. For the pre-treatment, Xyl-B was given via multiple injections (12.5, 25, and 50 mg·kg-1·d-1, ip) 48 h, 24 h and 30 min before ischemia. For the post-treatment, a single dose of Xyl-B (50 mg/kg, ip) was injected at 0, 1 or 2 h after the onset of ischemia. The regional cerebral perfusion was monitored using a laser-Doppler flowmeter. TTC staining was performed to determine the brain infarction volume. We found that both pre-treatment with Xyl-B (50 mg/kg) and post-treatment with Xyl-B (50 mg/kg) significantly reduced the infarct volume, but had no significant hemodynamic effects. Treatment with Xyl-B also significantly alleviated the neurological deficits in tMCAO mice. Furthermore, treatment with Xyl-B significantly attenuated ROS overproduction in brain tissues; increased the MnSOD protein levels, suppressed TLR4, NF-κB and iNOS protein levels; and downregulated the mRNA levels of proinflammatory cytokines, including IL-1ß, TNF-α, IL-6 and IFN-γ. Moreover, Xyl-B also protected blood-brain barrier integrity in tMCAO mice. In conclusion, Xyl-B administered within 2 h after the onset of stroke effectively protects against focal cerebral ischemia; the underlying mechanism may be related to suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway.

A novel mutation in the STK11 gene causes heritable Peutz-Jeghers syndrome - a case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease. CASE PRESENTATION: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease. CONCLUSION: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.

CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts.

Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts. Enforced-expression of circRNA_000203 could increase expressions of Col1a2, Col3a1 and α-SMA in mouse cardiac fibroblasts. RNA pull-down and RT-qPCR assay indicated that circRNA_000203 could specifically sponge miR-26b-5p. Dual luciferase reporter assay revealed that miR-26b-5p interacted with 3'UTRs of Col1a2 and CTGF, and circ_000203 could block the interactions of miR-26b-5p and 3'UTRs of Col1a2 and CTGF. Transfection of miR-26b-5p could post-transcriptionaly inhibit expressions of Col1a2 and CTGF, accompanied with the suppressions of Col3a1 and α-SMA in cardiac fibroblasts. Additionally, over-expression of circRNA_000203 could eliminate the anti-fibrosis effect of miR-26b-5p in cardiac fibroblasts. Together, our results reveal that suppressing the function of miR-26b-5p contributes to the pro-fibrosis effect of circRNA_000203 in cardiac fibroblasts.

Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy.

The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and ß-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.

Investigation of associations between ten polymorphisms and the risk of coronary artery disease in Southern Han Chinese.

A large-scale meta-analysis of 14 genome-wide association studies has identified and replicated a series of susceptibility polymorphisms for coronary artery disease (CAD) in European ancestry populations, but evidences for the associations of these loci with CAD in other ethnicities remain lacking. Herein we investigated the associations between ten (rs579459, rs12413409, rs964184, rs4773144, rs2895811, rs3825807, rs216172, rs12936587, rs46522 and rs3798220) of these loci and CAD in Southern Han Chinese (CHS). Genotyping was performed in 1716 CAD patients and 1572 controls using mass spectrography. Both allelic and genotypic associations of rs964184, rs2895811 and rs3798220 with CAD were significant, regardless of adjustment for covariates of gender, age, hypertension, type 2 diabetes, blood lipid profiles and smoking. Significant association of rs12413409 was initially not observed, but after the adjustment for the covariates, both allelic and genotypic associations were identified as significant. Neither allelic nor genotypic association of the other six polymorphisms with CAD was significant regardless of the adjustment. Our results indicated that four loci of the total 10 were associated with CAD in CHS. Therefore, some of the CAD-related loci in European ancestry populations are indeed susceptibility loci for the risk of CAD in Han Chinese.

Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population.

The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.

[Simulation and Observation of Vertical Cast-off Bloodstain Pattern].

OBJECTIVE: To observe the characteristics of vertical cast-off bloodstain pattern by different hitting-tools. METHODS: The regular hitting tools, a kitchen knife, a dirk, a plane set-hammer and an iron pipe, were selected. At a distance of 30 cm away from the wall, the hitting tool with 5 mL fresh chicken blood made the cast-off bloodstain from top to bottom. Then the holistic distribution characteristics (length, width and density) of cast-off bloodstain and morphology characteristics (length, width and contact angle) of first single cast-off bloodstain were analyzed. RESULTS: The distribution length of cast-off bloodstain formed by dirk was minimum (P < 0.05). The distribution width of cast-off bloodstain formed by kitchen knife was minimum (P < 0.05). Except the pair of kitchen knife and plane set-hammer, the distribution density between each two tools had statistical differences (P < 0.05). The length of first single cast-off bloodstain formed by plane set-hammer was longest compared (P < 0.05). The width of first single cast-off bloodstain had statistical differences between kitchen knife and plane set-hammer, and between dirk and plane set-hammer (P < 0.05). CONCLUSION: The type of hitting tool could be inferred by the specific characteristics of cast-off bloodstain pattern formed by every specific type of hitting tool in crime scene.

[Death caused by anaphylactic shock: a forensic pathological analysis of 142 cases].

OBJECTIVE: To explore the forensic pathological features of death caused by anaphylactic shock. METHODS: One hundred and forty-two death cases of anaphylactic shock were retrospectively analyzed. The IgE level in the serum of anaphylactic shock cases were statistically compared with that of 62 non-anaphylactic shock cases. RESULTS: Most cases (77.46%) of anaphylactic shock death occurred in the medical institutes, with intravenous drug administration accounting for 53.53% of anaphylactic shock death. ß-Lactam antibiotics, glucocorticoid and herbal medications were responsible for a significant proportion of such cases. Although characteristic histopathological changes were absent in vast majority of these anaphylactic shock cases, the differences of IgE levels in the serum between anaphylactic shock group and non-anaphylactic shock group were statistically significant (P<0.05). CONCLUSION: Combined information including clinical data, autopsy results, IgE level, and other specific test results should be evaluated together in the forensic pathological diagnosis of anaphylactic shock.

[Diatoms in drowned and postmortem immersed rabbits' lungs].

OBJECTIVE: To investigate the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs. METHODS: Sixty-two rabbits were randomly divided into drowning group (n = 30), postmortem immersion group (n = 30) and land death group (n=2), and the diatoms in each lung lobe were analyzed quantitatively and qualitatively by microwave digestion and scanning electron microscopy. RESULTS: In the drowning group, the diatoms were detected in each lung lobe with Cyclotella and Melosira in the majority. In the postmortem immersion group, Cyclotella was in the majority. And the diatoms weren't detected in some lung lobes in postmortem immersion. There were significant differences in the detection rates of upper lobe of left lung, middle lobe and cardiac lobe of right lung in two groups (P < 0.05). CONCLUSION: Based on the microwave digestion and scanning electron microscopy, the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs can be analyzed and used as references for testing theory.

[Epidemiological characters of Yunnan sudden death syndrome and its research progress].

Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown etiology, found mostly in central or northwestern mountain area (with altitude between 1,815 and 2,225 meters) of Yunnan province from June to September every year. It occurs mostly in young female adults, with high incidences in Lisu, Yi and Miao ethnics and high familial aggregation. The clinical manifestation of YSDS is changeful and the pathological characteristic is lack of specificity. The pathogenesis may be attributed to several factors including poor hygiene and lower socioeconomic conditions, lack of Selenium or Chromium, infection of Coxsackie B virus, mushroom consumption and special geological conditions. This article reviews the epidemiologic features, clinical manifestations, pathological features, etiology and hypothesis in order to provide clues for the research of YSDS.

The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery.

BACKGROUND: Previous studies have reported important roles of endothelin-1 (ET-1) and angiotensin II (Ang II) in the pathogenesis of atherosclerosis. However, the expression of these two proteins and the underlying mechanisms in human atherosclerotic coronary arteries are largely unknown. METHODS: We examined the expression of ET-1 and Ang II in pericardial fluid and coronary arteries from 25 individuals (n = 25) using enzyme-linked immuno sorbent assay (ELISA) and immunohistochemistry. Twelve patients died from acute coronary syndrome were classified as atherosclerotic plaque group (AP group) (n = 12), while 13 patients died from other causes were classified as non-AP group (n = 13). Meanwhile, we performed reverse transcription-polymerase chain reaction (RT-PCR) to measure the expression of six microRNAs targeting ET-1 in formalin-fixed, paraffin-embedded coronary arteries. RESULTS: Our data showed that ET-1 was significantly higher in both pericardial fluid and coronary arteries from AP group. However, Ang II showed no significant difference in pericardial fluid between the two groups, while it was even significantly lower in coronary arteries from AP group. Besides, miR-125a-5p, miR-155, and miR-199a/b-3p, which suppressed the expression of ET-1, were down-regulated in the coronary arteries from AP group. CONCLUSION: The up-regulation of ET-1, regulated by miR-125a-5p, miR-155, and miR-199a/b-3p, indicated that ET-1 played an important role in human coronary atherosclerosis. SUMMARY: We focused on the human coronary arteries with atherosclerotic plaques. The expression of ET-1, as well as its upstream miRNAs, was determined. Unlike any of previous study regarding miRNAs expression, we could exclude the discrepancy of artery-bed-specific miRNA expression. Besides, our data indicated, to some degree, that ET-1 might play a more vital role than Ang II in coronary atherosclerosis.

Inhibition of ovarian cancer cell proliferation by Pien Tze Huang via the AKT-mTOR pathway.

Pien Tze Huang (PZH) is a well-known Chinese medicine that has been used as a therapeutic drug in the treatment of a number of diseases, such as hepatocellular carcinoma and colon cancer. However, few studies have analyzed the effects of PZH on ovarian cancer cell proliferation. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, cell cycle and apoptosis rate analyses and western blotting were conducted to investigate the effects of PZH on the proliferation rate of ovarian cancer cells and its potential molecular pathway. The results showed that PZH inhibits the proliferation of the human ovarian cancer OVCAR-3 cell line by blocking the progression of the cell cycle from the G1 to S phase, however, PZH did not induce OVCAR-3 cell apoptosis. Increased PZH concentration may downregulate the expression of AKT, phosphorylated (p)-AKT, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the OVCAR-3 cell line. In addition, it was observed that PZH may suppress the protein expression of cyclin-dependent kinase (CDK)4 and CDK6. Overall, the results of the present study indicated that PZH may inhibit ovarian cancer cell proliferation by modulating the activity of the AKT-mTOR pathway.

EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion.

The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.