Showing papers in "BioScience Trends in 2019"

China has faster pace than Japan in population aging in next 25 years.

Abstract: The aging of a population structure is an inevitable path of demographic transition, as an inescapable result of decline in fertility rate and extension in life expectancy. Although demographic transition occurred earlier in Japan than in China, the two countries had similar patterns, both of which took a much shorter period of time than Western countries to complete demographic transition, as well as have been aging at a rapid speed that has rarely been seen in the world. Japan has the highest level of population aging in the world, and China has been experiencing a very fast pace of the population aging process and has the largest older population. Drawing upon data from World Population Prospects (2019), this paper compares changes in population aging in both China and Japan. Findings show that Japan's aging process is 30 years ahead of China, but China has been changing in a similar way as Japan. To be specific, both countries experienced four phases of the population aging process: accelerated development period, rapid development period, slow down period and high-level maintained period. In addition, both countries had a quick growing rate of population aging. It will take China 23 years and 10 years respectively for the aging rate increasing from 7% to 14% and then to 20%, while Japan took 24 and 11 years respectively, which is much shorter than developed countries in the West. Furthermore, China has a faster pace than Japan in population aging in the next 25 years. We found that from 2019-2044, China's aging rate, elderly dependency ratio, oldest-old coefficient and median age of population will increase 13.24 percent points, 24.21 percent points, 8.33 percent points, and 8.47 years, while the four indicators of Japan will increase 8.38 percent points, 22.52 percent points, 8.29 percent points, and 6.20 years, respectively.

Stem cell secretome as a new booster for regenerative medicine.

Abstract: Stem cells are an undifferentiated cell population that has the ability to develop into many different cell types and also has the ability to repair damaged tissues in some cases. For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of affected cells at the site of injury. This paracrine modulatory effect derives from secretome which comprises a diverse host of growth factors, cytokines, chemokines, angiogenic factors, and exosomes which are extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells and are from about 30 to several hundred nanometers in diameter. The role of these factors is being increasingly recognized as key to the regulation of many physiological processes including leading endogenous and progenitor cells to sites of injury as well as mediating apoptosis, proliferation, migration, and angiogenesis. In reality, the immunomodulatory and paracrine role of these factors may mainly account for the therapeutic effects of stem cells and a number of in vitro and in vivo researches have proved limited stem cell engraftment at the site of injury. As a cell-free way for regenerative medicine therapies, stem cell secretome has shown great potential in a variety of clinical applications including prevention of cardiac disfunction, neurodegenerative disease, type 1 diabetes, hair loss, tumors, and joint osteoarthritis.

The community-based integrated care system in Japan: Health care and nursing care challenges posed by super-aged society.

Abstract: Japan is experiencing unprecedented aging of its population. People age 65 years or older accounted for 28.1% of the total population in 2018, and that proportion is expected to reach 33.3% in 2036 and 38.4% in 2065. In 2017, the average life expectancy in Japan was 81.09 years for men and 87.26 years for women. By 2065, it is expected to reach 84.95 years for men and 91.35 years for women. Population aging affects health and long-term care systems. The government proposed the establishment of "a community-based integrated care system" by 2025 with the purpose of comprehensively ensuring the provision of health care, nursing care, preventive care, housing, and livelihood support. This will require health care and nursing care professionals who are capable of fully understanding the physical and mental characteristics of elderly people and the fostering of organic collaboration with others professionals in the community-based integrated care system. A department of gerontology or geriatric medicine is desired to be established in each medical school to teach students medicine and efficient medical care, to conduct research, and to develop personnel to facilitate this paradigm shift. In 2018, there were 263 colleges of nursing with an admissions capacity of 23,667. In Japan, Certified Nurse Specialists can specialize in 13 areas as of December 2016. The number of Certified Nurse Specialists increased to 2,279 as of December 2018. One hundred and forty-four of those specialists specialized in Gerontological Nursing while 53 specialized in Home Care Nursing. The number of nurses specializing in Gerontological Nursing and Home Care Nursing is desired to be increased in order to implement and improve community-based comprehensive care.

A review of traditional Chinese medicine for treatment of glioblastoma.

Abstract: Glioblastoma (GBM) is the most common primary malignant intracranial tumor. Due to its high morbidity, high mortality, high recurrence rate, and low cure rate, it has brought great difficulty for treatment. Although the current treatment is multimodal, including surgical resection, radiotherapy, and chemotherapy, it does not significantly improve survival time. The dismal prognosis and inevitable recurrence as well as resistance to chemoradiotherapy may be related to its highly cellular heterogeneity and multiple subclonal populations. Traditional Chinese medicine has its own unique advantages in the prevention and treatment of it. A comprehensive literature search of anti-glioblastoma active ingredients and derivatives from traditional Chinese medicine was carried out in literature published in PubMed, Scopus, Web of Science Cochrane library, CNKI, Wanfang, and VIP database. Hence, this article systematically reviews experimental research progress of some traditional Chinese medicine in treatment of glioblastoma from two aspects: strengthening vital qi and eliminating pathogenic qi. Among, strengthening vital qi medicine includes panax ginseng, licorice, lycium barbarum, angelica sinensis; eliminating pathogenic medicine includes salvia miltiorrhiza bunge, scutellaria baicalensis, coptis rhizoma, thunder god vine, and sophora flavescens. We found that the same active ingredient can act on different signaling pathways, such as ginsenoside Rg3 inhibited proliferation and induced apoptosis via the AKT, MEK signal pathway. Hence, this multi-target, multi-level pathway may bring on a new dawn for the treatment of glioblastoma.

Circular RNA profiling reveals circRNA1656 as a novel biomarker in high grade serous ovarian cancer.

Abstract: Circular RNA (circRNA) is a class of endogenous non-coding RNAs that are closely related to the pathogenesis of many human diseases, particularly cancer. However, the characterization of circRNAs in high-grade serous ovarian cancer (HGSOC) remains unknown. This study aimed to investigate the expression profile of circRNAs in HGSOC. Expression profiles of circRNAs differential expression based on circRNAs High-throughput sequencing were identified in 3 HGSOC specimens and 3 normal ovarian tissues. A total of 710 differentially expressed circRNAs were found (354 expressions up-regulated and 356 expressions down-regulated). CircRNA sequencing data were verified by qRT-PCR in HGSOC tissue and benign ovarian lesions. Differential expression of 7 circRNAs (circRNA385, circRNA2058, circRNA3336, circRNA2606, circRNA1656, circRNA1312 and circRNA7474) in HGSOC tissue was confirmed by qRT-PCR. Among them, circRNA1656 showed the highest fold change. qRT-PCR was used to verify the expression of circRNA1656 in ovarian cancer cell lines. In order to analyze the relationship between circRNA1656 expression and clinical pathological biological characteristics of HGSOC, qRT-PCR was used to verify the expression of circRNA1656 in 60 HGSOC tissues compared with 60 benign ovarian lesions. The expression of circRNA1656 was down-regulated in HGSOC tissues and ovarian cancer cell lines, and correlated with the FIGO stage of HGSOC. circRNA1656 has the potential to serve as a novel tumor marker for HGSOC.

Anti-inflammatory, anti-oxidative stress and novel therapeutic targets for cholestatic liver injury

Abstract: Cholestasis is a pathological process in which bile drainage is poor for a variety of reasons. Many studies have shown that cholestatic liver injury is a neutrophil-mediated inflammatory response, and oxidative stress induced by neutrophils is the main mechanism of liver cell death. The literature summarizes the bile acid signaling pathway, the neutrophil chemotaxis recruitment process during cholestasis, and the oxidative stress damage produced by neutrophil activation, summarizes the latest research progress. Sphingosine-1-phosphate receptor (S1PR) is a potential therapeutic target for cholestasis that reduces neutrophil aggregation without inhibiting systemic immune status. Early growth response factor 1 (Egr-1) may play a central role in the inflammation induced by cholestasis, and it is also a potential therapeutic target to inhibit the inflammation induced by cholestasis. Strengthening the antioxidant system of hepatocytes to cope with oxidative stress of neutrophils is a feasible treatment for cholestatic liver injury.

Progress on drug pricing negotiations in China

Abstract: On November 28th, 2019, the National Healthcare Security Administration (NHSA) and the Ministry of Human Resources and Social Security (MOHRSS) of China announced the results of drug pricing negotiations. Seventy first-negotiated drugs with 60.7% average price decrease and twenty-seven re-negotiated medicines with 26.4% average price fall, involving 11 disease categories, were successfully incorporated into National Reimbursement Drug List (NRDL). Medicines that successfully get accessed to NRDL are mostly new listings with high clinical value, and more than half of them are manufactured by Chinese enterprises. Compared to the negotiated drug list of 2017, the biggest increase in western medicines is the digestive system medications (10 drugs added), and the traditional Chinese medicine is internal medicine (17 drugs added). The negotiation follows the process including preparation, examination, negotiation, and announcement. There are several innovations in the procedure, such as the parallel calculation of the floor price, the introduction to competitive negotiations, allowing companies to apply for price confidentiality, and increasing government-enterprise communication before negotiations. Incorporating patent drugs into NRDL by negotiation not only helps patients reduce the economic burden, but also encourages pharmaceutical companies to innovate.

Lab on the eye: A review of tear-based wearable devices for medical use and health management.

Abstract: Wearable sensors have garnered considerable interest because of their great promise in terms of personalized health and disease management. Tears are a superior target for wireless, non-invasive wearable devices, and tear-based platforms have developed rapidly over the past decade. Although an increasing number of tear analytes have been found to be associated with multiple diseases, glucose still serves as a main target for tear-based wearable devices. There has been much investment and efforts to develop tear-based wearable biosensors, with contact lens-based and spring-like sensors flourishing commercially. Current efforts have moved past ocular and systematic disease markers to nutrients and chemicals. Moreover, tear-based wearable devices also have the potential to treat some ocular diseases. This review discusses aspects of tear-based wearable devices and it emphasizes that strict clinical validation is needed before such platforms enter the market. Multifunctional and theranostic strategies would further broaden their clinical use in the future.

The pro-tumor effect and the anti-tumor effect of neutrophils extracellular traps.

Abstract: Significant advances in our understanding of neutrophil biology were made in the past several years. A newly discovered mechanism was discovered, the formation of neutrophils extracellular traps (NETs). The structure of NETs is composed of the DNA strand and neutrophil granule proteins. NETs were found to have an association with tumor progression. This review highlights the latest knowledge about the controversial effect on tumors of NETs. Pro-tumor and anti-tumor effects are described respectively. The probable mechanisms of the anti-tumor effect are related to its direct killing of cancer cells or stimulation of the immune system to fight against the tumor. The pro-tumor effect has a correlation with matrix metalloproteinase 9 (MMP-9), cathepsin G, and neutrophil elastase (NE). Moreover, the structure of the NETs makes it able to catch the circulating tumor cells, which could lead to metastasis. This review summarizes our knowledge about the proven roles of NETs in the progression of cancer with particular focus on the components of the NETs, and considers NETs as a potential target for cancer therapy.

The toxicity and safety of traditional Chinese medicines: Please treat with rationality

Abstract: For a long time, many people have believed that traditional Chinese medicines (TCMs) are safe because they derive from natural products. However, this belief has been greatly challenged in recent years especially after some reports on aristolochic acid involved in the genesis of cancer. According to the Chinese pharmacopoeia, many TCMs are known to be toxic, causing damage to the nervous, liver, renal, respiratory, and reproductive system. How to reduce the toxicity of TCMs and how to avoid abuse of TCMs in daily practice is the question? Here, we will give a brief summary and some tips on these issues. First, the accurate differentiation of a specific syndrome is the foundation of an effective and individualized treatment strategy, as well as the key to applying TCMs. Second, through standard processing, proper compatibility, rational decoction, and appropriate dose for TCMs, the harm of TCMs can be effectively avoided. Third, it should be remembered that Chinese herbs cannot be taken continuously as dietary supplements. Finally, Chinese patent medicines should be used with caution. In addition, the dosage of TCMs should not exceed the limit prescribed by the current China Pharmacopoeia, which will ensure the balance of efficacy and toxicity. Taken together, it is necessary to treat the toxicity and safety of TCMs with rationality. The more toxicity we can find, the more safety patients will have.

Daucosterol induces autophagic-dependent apoptosis in prostate cancer via JNK activation.

Abstract: Plant sterols (phytosterols) have been widely accepted as a natural anti-cancer agent in multiple malignant tumors. This study was designed to investigate the functions of daucosterol in prostate cancer progression and its possible molecular mechanisms. Our results showed that daucosterol inhibited cell proliferation and induced cell cycle arrest. Moreover, daucosterol treatment obviously promoted apoptosis and autophagy. An autophagy inhibitor, 3-methyladenine (3-MA) was proved to counteract daucosterol-triggered autophagy, growth inhibition, and apoptosis, indicating that daucosterol-induced apoptotic response was dependent on autophagy. Additionally, treatment with daucosterol resulted in increased phosphorylation of c-Jun N-terminal kinase (JNK). Furthermore, pre-treatment with a JNK-specific inhibitor SP600125 abated daucosterol-elicited autophagy and apoptotic cell death. Taken together, our findings demonstrated that daucosterol blocked prostate cancer growth at least partly through inducing autophagic-dependent apoptosis via activating JNK signaling, providing a promising candidate for the development of antitumor drugs in prostate cancer treatment.

The clinical safety and efficacy of conventional transcatheter arterial chemoembolization and drug-eluting beads-transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A meta-analysis

Abstract: Transcatheter arterial chemoembolization (TACE) plays an important role in the treatment of unresectable liver cancer. We conducted this meta-analysis to compare the clinical safety and efficacy of conventional TACE (C-TACE) and drug-eluting beads (DEB)-TACE. A search for those procedures was performed using the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis of patients who underwent C-TACE or DEB-TACE was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of 334 studies, 30 were analyzed. The complete response rate, disease control rate, objective response rate, 3-year survival rate, and non-response rate were significantly higher in patients who underwent DEB-TACE than those in patients who underwent C-TACE. The 1-year survival rate, 2-year survival rate, 30-day mortality rate, complete response rate, disease control rate, complete necrosis rate, non-response rate, objective response rate, progressive disease rate, and recurrence did not differ significantly between patients who underwent C-TACE and patients who underwent DEB-TACE. Patients who undergo DEB-TACE might have a higher complete response rate, disease control rate, and 3-year survival rate than patients who undergo C-TACE. Safety did not differ significantly between C-TACE and DEB-TACE.

Overview on social security system of rare diseases in China

Abstract: China has initiated the special security project for rare diseases from the national strategic level since 2018. Chinese government has formulated China's First List of Rare Diseases (121 diseases included), established Expert Committee of Diagnosis, Treatment and Security of Rare Diseases and China Alliance of Rare Diseases. The government also encouraged all the provinces to include the security plan and strategies of rare diseases into key work and promoted the establishment of rare diseases clinical research center and the formulation of diagnosis and treatment guidelines. All these actions led to the further improvement of scientific research ability and diagnosis and treatment ability. In terms of the treatment drug of the 121 diseases in China's First List of Rare Diseases, 83 of them are on the market in China and 50 have been included in the national medical insurance accompanied with the tax reduction policy on rare diseases drug and several charity foundations and enterprise donation programs were developed so that drug availability and accessibility for patients are increased. However, there is no clear definition and corresponding coding of rare diseases; the economic burden of most rare diseases could not be calculated accurately because of the difficulty in diagnosis and misclassification. Regarding the service provision system, social security system of rare diseases in China needs further improvement because of the rather few kinds of rare diseases involved in the screening, low level of diagnostic ability, rather few rehabilitation programs and the lack of social caring and knowledge training. It is necessary for China to provide comprehensive and well-rounded health care and social caring for rare diseases patients. Since the formulation and implementation conditions of the policy are different among different regions, the pilot should be carried out first in regions with desired qualifications when China is formulating the rare diseases policy and then a mature national plan should be developed.

IFITM3 upregulates c-myc expression to promote hepatocellular carcinoma proliferation via the ERK1/2 signalling pathway.

Abstract: Interferon-induced transmembrane protein 3 (IFITM3) is associated with cancer development. Proto-oncogene c-myc can promote tumor proliferation. However, collections of IFITM3 and c-myc in hepatocellular carcinoma (HCC) and the potential role and mechanisms of IFITM3 in c-myc-mediated tumor proliferation remain unclear. In this study, we investigated a positive correlation between the expression of IFITM3 and c-myc in HCC. The down-regulation of IFITM3 significantly reduced c-myc expression and inhibited the proliferation of HCC in vitro and in vivo. In addition, upregulated c-myc expression restored the decrease in cell proliferation caused by the downregulation of IFITM3, while downregulation of c-myc reduced the proliferation of HCC enhanced by IFITM3. Mechanistically, IFITM3 regulates c-myc expression via the ERK1/2 signalling pathway. In conclusion, a novel path of IFITM3-ERK1/2-c-myc regulatory circuitry was identified, and its dysfunction may lead to HCC tumorigenesis.

Sperm DNA fragmentation valued by SCSA and its correlation with conventional sperm parameters in male partner of recurrent spontaneous abortion couple.

Abstract: The objective of this study is to evaluate the predictive value of sperm DNA fragmentation Index (DFI) in unexplained recurrent spontaneous abortion (RSA) and to investigate its correlation with conventional sperm parameters. Besides, we aimed to reveal the necessity of establishing a DFI clinical threshold of each laboratory for the prognostic diagnosis of RSA and establish our own DFI threshold. Semen samples were collected from male partners of RSA patients (n = 139) and healthy recent fathers (control, n = 200). DFI was tested using SCSA and conventional semen analysis was performed using an automatic semen analyzer. The DFI value and distribution were compared between the two groups using corresponding statistical software. The diagnostic threshold value was established by ROC curve. The correlation between DFI and the conventional semen parameters of the 139 cases was further analyzed using Student's t test and Mann-Whitney U test. Our result showed that DFI was significantly higher in RSA patients compared with normal donor controls. We established our own DFI threshold at 13.59%. There was only a weak partial correlation between DFI values and conventional sperm analysis parameters. Our present study suggested that DFI might be used as a valuable predictor for RSA independent of conventional sperm parameters. Additionally, we recommend that each laboratory should establish its own clinical DFI threshold for more precise prediction of RSA and we recommend that sperm DNA fragmentation test should be included in complete sperm quality assessment in addition to conventional semen analysis for RSA male partners.

Programmed death ligand-1, tumor infiltrating lymphocytes and HLA expression in Chinese extrahepatic cholangiocarcinoma patients: Possible immunotherapy implications.

Abstract: Immunotherapy might be an effective treatment in extrahepatic cholangiocarcinoma (eCCA), a tumor with extremely limited therapeutic options. Our study is to characterize the programmed death ligand-1 (PD-L1) protein expression and cancer microenvironment profiles in surgically resected eCCA samples. PD-L1 positivity was observed on tumor cells (32.3%) as well as on tumor-associated macrophages (74.2%). PD-L1 expression by eCCA correlated significantly with immune parameters such as intra-tumoral CD3+ tumor infiltrating lymphocytes (TILs) density (P = 0.002), intra-tumoral CD8+ TILs density (P < 0.001), and the expression pattern of human leukocyte antigen (HLA) class I (P < 0.001). Immunofluorescence showed that PD-L1 positive tumor cells were adjacent to PD-1 positive cells and the stroma covered with interferon-γ. Correlation with clinicopathological parameters and survival analyses revealed that PD-L1 positivity in eCCA was related to the absence of venous invasion (P = 0.030), improved overall survival (P = 0.020) and progressionfree survival (P = 0.011). HLA class I molecules defect, which is an important mechanism of immune evasion, was frequently observed in eCCA (50.0%) and was associated with a decreased number of intra-tumoral CD8+ TIL density (P = 0.028). Additionally, the presence of unusually high numbers of tumor-associated macrophages (TAMs) subsets M2 in most of eCCA (74.2%) was noted. Our study indicated that PD-L1 expression in association with intra-tumoral TILs infiltration and HLA class I expression in 32.3% of the eCCA reflects an active immune microenvironment potentially responsive to PD-1/PD-L1 inhibitors. In addition, the combination of macrophage-targeting agents may provide therapeutic synergy for future immunotherapy.

Efficacy and safety of external-beam radiation therapy for hepatocellular carcinoma: An overview of current evidence according to the different target population.

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.

Neuron loss and dysfunctionality in hippocampus explain aircraft noise induced working memory impairment: a resting-state fMRI study on military pilots.

Abstract: Long-term aircraft noise exposure may cast a detrimental effect upon the working memory of military pilots, and the brain structural and functional bases of noise related cognitive impairment remains unclear. In this study, we enrolled 30 fighter jet pilots and 30 matched controls. The working memory performance of the subjects was measured with a neurobehavioral test battery including immediate verbal/visual memory and delayed verbal/visual memory tests. Structural MRI and resting-state functional magnetic resonance imaging (rs-fMRI) were utilized to quantify brain grey matter volumes (GMV), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) differences between the two groups. Furthermore, correlation analyses were performed to find the association between the neural imaging changes with individual neurobehavioral performance. The military pilots showed significantly lower accuracy in delayed verbal and visual memory tests in comparison to the controls, indicating a potential working memory deficit in this population. Structural MRI data and rs-fMRI data showed that the pilots displayed markedly decreased GMVs, ReHo and ALFF signals in the left hippocampus, suggesting neuron dysfunction of the hippocampus. Besides, ReHo and ALFF/fALFF analysis also revealed reduced ReHo in the left amygdala, left thalamus, left superior temporal gyrus and right superior/middle frontal gyrus, indicating disrupted local neural activity under chronic noise exposure. Furthermore, Spearman correlation analysis proved that the GMV and ReHo of left hippocampus were significantly associated with working memory accuracy. This study provided direct evidence of dysfunctional hippocampus serving as the structural and functional bases for neuropsychological impairment under aircraft noise exposure.

Dioscin improves postmenopausal osteoporosis through inducing bone formation and inhibiting apoptosis in ovariectomized rats.

Abstract: Postmenopausal osteoporosis (PMO) has become a public health problem worldwide. Hormonal replacement therapy (HRT) is the most popular treatment for PMO at present, but the side effects, including increased risk of endometrial cancer and breast cancer, limit its clinical use. Therefore, finding a new medication with high efficiency and less side-effects is urgently required. Dioscin is the main ingredient of some medicinal plants such as Dioscorea nipponica Makino and Dioscorea zingiberensis Wrigh. It is reported that dioscin has anti-tumoral and anti-atherosclerotic activity as well as an inhibitory effect on hepatic fibrosis. In this study, the effects of dioscin on PMO were examined and the mechanisms were analyzed. The results indicated that the bone mineral density and ultimate load of PMO rats were increased after being treated with dioscin. H&E staining and immunohistochemical staining showed the bone trabeculae formation and bone differentiation of PMO rats were promoted by dioscin. Western blots revealed that dioscin could activate the PI3K/P38/AKT signaling pathway and inhibit the apoptosis signaling pathway in bone tissue cells of PMO rats. In addition, MTT assays showed that MC3T3-E1 cell viability could be improved by dioscin. These results suggest dioscin is a potential therapeutic reagent for osteoporosis and deserves further investigation.

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway.

Abstract: Cordycepin, a derivative of nucleoside adenosine, is one of the active ingredients extracted from the fungi of genus Cordyceps, which have been used for traditional herbal remedies. In this study, we examined the effect of cordycepin on the proliferation and apoptosis of human bladder cancer T24 cells and its mechanism of action. Cordycepin treatment significantly reduced the cell survival rate of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptosis. Cordycepin activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, cordycepin increased the Bax/Bcl-2 ratio and truncation of Bid, and destroyed the integrity of mitochondria, which contributed to the cytosolic release of cytochrome c. Moreover, cordycepin effectively inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of cordycepin. Cordycepin further enhanced the intracellular levels of reactive oxygen species (ROS), while the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished cordycepin-induced mitochondrial dysfunction and growth inhibition, and also blocked the inactivation of PI3K/Akt signaling pathway. Furthermore, the presence of NAC significantly attenuated the enhanced apoptotic cell death and reduction of cell viability by treatment with cordycepin and LY294002. Collectively, the data indicate that cordycepin induces apoptosis through the activation of extrinsic and intrinsic apoptosis pathways and the ROS-dependent inactivation of PI3K/Akt signaling in human bladder cancer T24 cells.

Preoperative evaluation of the degree of liver fibrosis based on matter-element analysis using serological indicators in patients with hepatocellular carcinoma.

Abstract: Evaluation of the degree of liver fibrosis is an important basis for the clinical diagnosis and treatment of patients with hepatocellular carcinoma (HCC). It is meaningful to make a preoperative evaluation with non-invasive methods. In the current study, 12 commonly used preoperative serological indicators from 161 HCC patients with different degree of liver fibrosis were collected retrospectively, and 8 of the indicators (ALB, PA, TBil, INR, AST, GGT, ALP, and PT) were ultimately used in matter-element analysis to create a formula. The relationship between those results and the histological sub-classification of the Laennec liver fibrosis scoring system was analyzed. The calculated value of R from this formula will indicate the differing degree of liver fibrosis in a patient: i) the value of 0.802 ≤ R < 1 indicates the early stage of liver cirrhosis, which corresponds to Laennec stages 0-3; ii) the value of 0.752 ≤ R < 0.802 indicates the mild stage of liver cirrhosis, which corresponds to Laennec stage 4A; iii) the value of 0.698 ≤ R < 0.752 indicates the moderate stage of liver cirrhosis, which corresponds to Laennec stage 4B; and iv) the value of 0.444 ≤ R < 0.698 indicates the severe stage of liver cirrhosis, which corresponds to Laennec stage 4C. The hope is that this formula for preoperative evaluation of the degree of liver fibrosis using non-invasive methods would be useful in the clinical diagnosis and treatment of patients with HCC in the future.

Treatment modalities and relative survival in patients with brain metastasis from colorectal cancer.

Abstract: Standard treatment options for brain metastases (BM) from colorectal cancer (CRC) are controversial. The purpose of this study was to evaluate the efficacy of multidisciplinary treatment modalities and provide optimal therapeutic strategies for selected patients with different clinical characteristics. All eligible patients diagnosed with BM from CRC during the past two decades (1997-2016) were identified in our center. Clinical characteristics, treatment modalities and relative survival were retrospectively analyzed. Median overall survival after the identification of BM was 6 months. The 1- and 2- year survival rates were 29.40% and 5.70%, respectively. On multivariate analysis, the number of BMs, Karnofsky performance score and the treatment modalities were found to be independent prognostic factors (the p-value was 0.006, 0.001 and 70, neurosurgery combined with chemotherapy could provide an additional survival benefit. For patients with multiple brain metastases or KPS ≤ 70, radiotherapy plus chemotherapy may be appropriate.

A multiplex loop-mediated isothermal amplification assay for rapid detection of Bacillus cereus and Staphylococcus aureus.

Abstract: Bacillus cereus (B. cereus) and Staphylococcus aureus (S. aureus) are major human food-borne pathogens that may produce a variety of toxins and cause diarrhea, food poisoning, and even death. In order to monitor and prevent the spread of these pathogens, a multiplex loop-mediated isothermal amplification (multi-LAMP) assay was developed to simultaneously and rapidly detect B. cereus and S. aureus. The sensitivity and specificity of the loop-mediated isothermal amplification (LAMP) reactions were determined via electrophoresis. The multi-LAMP showed 100% inclusivity and exclusivity, the sensitivity was 10 fg/μL and was 10 times more sensitive than that of polymerase chain reaction (PCR), the results were consistent with those of conventional PCR assay, and the entire assay should be finished within 40 min. This multi-LAMP assay was confirmed as a rapid and reliable diagnostic technique upon application for clinical samples and food samples. To our knowledge, this is the first study to report the application of multi-LAMP to detect B. cereus and S. aureus.

Recent progress in induced pluripotent stem cell-derived cardiac cell sheets for tissue engineering.

Abstract: The past decade has witnessed remarkable development in tissue engineering technologies and stem cells. Our lab has developed a novel technology - "cell sheet technology" for tissue engineering. After the confluent cells are cultured on an innovative temperature-responsive culture dish, the cells can be harvested as an intact sheet by lowering temperature. We have successfully created multiple cell sheet-based tissues for therapies of a vast variety of diseases, in particular, myocardial diseases. On the other side, the discovery of human induced pluripotent stem cells (hiPSC) enables stable production of defined tissue-specific cell types and thus makes it possible to regenerate tissues or even organs for clinical application and in vitro drug screening/disease modeling. Recently, we have combined cell sheet technology and hiPSC-derived cardiac cells for fabrication of functional human cardiac tissues. This review summarizes ongoing challenges in this field and our progresses in solving issues, such as large scale culture of hiPSC-derived cardiac cells, elimination of undifferentiated iPSCs to decrease the risk of tumor formation as well as myocardial tissue fabrication technologies.

IL16 deficiency enhances Th1 and cytotoxic T lymphocyte response against influenza A virus infection

Abstract: Influenza A virus (IAV) is the major cause of seasonal epidemics and flu outbreaks worldwide. Given that interleukin 16 (IL16) can regulate T cell function and is one of the signature markers for virus infection including IAV infection, the impact of IL16 on IAV-induced T cell immune response hasn't been elucidated yet. In this paper, we infected wild type and IL16 knockout (KO) mice with IAV and analyzed the immunity of mice by flow cytometry. We observed an increase in the percentage of T helper (Th) 1 cells in the spleens of IL16 KO mice and elevation of IFN-γ and TNF-ɑ secretion from CD8+ T cells in the lungs and spleens of IL16 KO mice in response to IAV infection. Moreover, the expression of major histocompatibility complex II which represents the maturation of dendritic cells (DCs) was upregulated in the lungs of IL16 KO mice. Taken together, our study suggests that IL16 deficiency enhanced Th1 and cytotoxic T lymphocyte response as well as DC maturation upon IAV infection, which provides new insight into the host regulation of T cell immune responses during IAV infection.

By regulating miR-182-5p/BCL10/CYCS, sufentanil reduces the apoptosis of umbilical cord mesenchymal stem cells caused by ropivacaine.

Abstract: Sufentanil is a type of opioid analgesic and is usually used to facilitate painless labor in combination with the local anesthetic ropivacaine. One aim of the current study was to investigate the effects of sufentanil and ropivacaine on umbilical cord mesenchymal stem cells (UCMSCs). A second aim of this study was to determine whether sufentanil attenuated the cytotoxicity of ropivacaine in vitro. UCMSCs were divided into 3 groups: one was treated with ropivacaine at a concentration of 50, 100, 200, or 400 μg/mL, another was treated with sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L, and a third was treated with a combination of ropivacaine at a concentration of 200 μg/mL and sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L. Results indicated that cell proliferation decreased in cells treated with ropivacaine while it increased in cells treated with sufentanil. In addition, sufentanil limited the inhibitory effect of ropivacaine on UCMSC growth in a dose- and time-dependent manner. Combined treatment with ropivacaine at a concentration of 200 μg/mL and sufentanil at a concentration of 500 nmol/L decreased the proportion of dead and apoptotic UCMSCs, and fewer cells were arrested in the S phase compared to cells treated with ropivacaine. Sufentanil inhibited the apoptosis induced by ropivacaine by increasing miR-182-5p, which regulated the expression of mRNA of the pro-apoptotic genes B-cell lymphoma/leukemia 10 (BCL10) and cytochrome c, somatic (CYCS). Sufentanil also increased the expression of mRNA of anti-apoptotic genes. In short, ropivacaine inhibits the cell viability and induces the apoptosis of UCMSCs in vitro while sufentanil attenuates this apoptosis by regulating miR182-5p/BCL10/CYCS.

Chinese herbal medicine for acute upper respiratory tract infections and reproductive safety: A systematic review.

Abstract: Acute upper respiratory tract infections (AURTIs) are common and self-limited in people with normal immunity but sometimes lead to poor clinical outcomes under specific conditions such as pregnancy if not treated appropriately. Chinese herbal medicines (CHM), which are widely used to treat AURTIs, have proven to be effective in preclinical and clinical studies. This review focuses on the bioactivities of typical CHM and the adverse reactions they cause, and especially issues with reproductive safety when treating AURTIs. The main mechanisms for clinical efficacy may include anti-viral, anti-bacterial, anti-inflammatory, antipyretic, and immunomodulatory action as indicated by preclinical evidence. Most clinical trials indicate that CHM shortens the natural course of AURTIs and that it relieves related symptoms such as a fever, headaches, coughing, myalgia, a cold, sore throat, and a nasal obstruction. However, some CHM have a range of adverse effects and potentially affect reproduction from endocrinal secretion to embryo development while others do not. Therefore, clinical adverse reactions and preclinical studies on the toxicity of CHM are discussed. More reliable evidence is required to conclude that CHM are efficacious and safe for pregnant women with AURTIs. This review should help to promote advances in the research on and development of CHM as alternative treatments for AURTIs and offer insight into strategies to manage the safety of CHM during clinical use.

A Clinical scoring model to predict mortality in HIV/TB co-infected patients at end stage of AIDS in China: An observational cohort study.

Abstract: We construct and validate a non-invasive clinical scoring model to predict mortality in HIV/TB patients at end stage of AIDS in China. There were 1,007 HIV/TB patients admitted to Beijing Ditan Hospital from August 2009 to January 2018 included in this study, who were randomly assigned to form derivation cohort and validation cohort. A clinical scoring model was developed based on predictors associated with mortality identified with Cox proportional hazard models. The discrimination and accuracy of model were further validated using the area under the ROC curves. The derivation and validation cohort consisted of 807 and 200 patients in 8:2 ratio, respectively. In derivation cohort, anemia (HGB < 90g/L), tuberculous meningitis, severe pneumonia, hypoalbuminemia, unexplained infections or space-occupying lesions, and malignancies remained independent risk factors of mortality in HIV/TB co-infected patients, and included in this clinical scoring model. The model indicated good discrimination, including AUC = 0.858 (95% CI: 0.782-0.943) in the derivation cohort, and AUC = 0.867 (95% CI: 0.832-0.902) in validation cohort, respectively. The predicted scores were categorized into two groups to predict the mortality: low-risk (0-2 points with mortality with 3.6-9.1%) and high-risk (4-16 points with mortality with 26.42-74.62%), in which 54.55% and 74.62% of patients with score of 5 to 11 and 12-16 were died among high-risk group. Kaplan-Meier curve indicated a significant difference in the cumulative mortality in the two groups by log-rank test (p < 0.001). A clinical scoring model to assess the prognosis in HIV/TB patients at end stage of AIDS was constructed based on simple laboratory and clinical features available at admission, which may be an easy-to-use tool for physicians to evaluate the prognosis and treatment outcome in HIV/TB co-infected patients. The model was also applicable for predicting the death of end-stage HIV/TB patients within a 12 months period after discharge.

Challenges and advances in stem cell therapy

Abstract: After decades of research, stem cells have shown tremendous promise to treat a range of diseases, such as heart disease, diabetes, and neurodegenerative disease. However, many challenges remain in their transformation from bench to bedside, such as the potential risk of tumorigenicity from undifferentiated human induced pluripotent stem cells (hiPSC), the lack of large-scale culture systems for clinical treatment, and the inconvenience of cell therapy itself. "Cell sheet technology" and secretome therapy represent advances in these regards. With gradual breakthroughs in theory and technology, stem cell therapy will lead to a new medical revolution in the coming era.

Design, synthesis and biological evaluation of 4-piperidin-4-yl-triazole derivatives as novel histone deacetylase inhibitors.

Abstract: Histone deacetylase is an important member of epigenetics and a well validated target for anti-cancer drug discovery. In this study, we designed and synthesized a series of twenty-one novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward histone deacetylases at the concentration of 1 μM. Among them, the inhibition rates of two compounds MH1-18 and MH1-21 exceeded 90%. Furthermore, these two compounds selectively inhibited the activity of histone deacetylase 6 with low IC50 values. The high potency of them toward histone deacetylase 6 was rationalized by molecular docking studies. We found that MH1-18 and MH1-21 moderately inhibited the proliferation of four human cancer cell lines SGC-7901, NCI-H226, MCF-7, and HL-60. However, MH1-21 showed potent efficacy in suppressing the migration of MCF-7 cells. Results obtained in the current study shed light on designing potent HDAC6 inhibitors as anti-cancer agents.