Traditional Chinese medicine (TCM), as a type of complementary and alternative medicine (CAM), is a sophisticated and time-honored form of healthcare in China. Many TCMs are widely used to treat hepatitis B and hepatitis C in countries like China, Japan, and South Korea. Since conventional clinical preparations like interferon-α cause obvious dose-dependent adverse reactions and drug resistance, TCMs and related bioactive compounds have garnered increasing attention from physicians and medical researchers. Thus far, a number of TCMs and compounds have been used to inhibit the hepatitis B virus (HBV) or hepatitis C virus (HCV) in vitro, in vivo, and even in clinical trials. The current review summarizes TCMs and related compounds that have been used to inhibit HBV or HCV. Most of these medicines are derived from herbs. HepG2.2.15 cells have been used to study HBV in vitro and Huh7.5 cells have been similarly used to study HCV. Ducks have been used to study the anti-HBV effect of new medication in vivo, but there are few animal models for anti-HCV research at the present time. Thus far, a number of preclinical studies have been conducted but few clinical trials have been conducted. In addition, a few chemically modified compounds have displayed greater efficacy than natural products. However, advances in TCM research are hampered by mechanisms of action of many bioactive compounds that have yet to be identified. In short, TCMs and related active compounds are a CAM that could be used to treat HBV and HCV infections.
Early specific diagnosis and effective treatment of hepatocellular carcinoma (HCC) are crucial. Expression of membrane-associated heparan sulfate proteoglycan glypican-3 (GPC-3) was recently found to increase as part of the malignant transformation of hepatocytes, and this increase is especially marked in patients with hepatitis B virus (HBV) infection, periportal cancerous embolus, or extra-hepatic metastasis. According to data from basic and clinical studies, the oncofetal antigen GPC-3 is a highly specific diagnostic biomarker of HCC and an indicator of its prognosis, and GPC-3 is also a promising target molecule for HCC gene therapy since it may play a crucial role in cell proliferation, metastasis, and invasion and it may mediate oncogenesis and oncogenic signaling pathways. This review summarizes recent advances in the use of oncofetal antigen GPC-3 to diagnose HBV-related HCC, estimate its prognosis, and its targeted therapy.
Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for severe emphysema, providing treatment options for patients who are unable to undergo lung volume reduction surgery (LVRS) or lung transplantation. Current BLVR techniques include bronchoscopic volume reduction with valve implants, use of a lung volume reduction coil (LVRC), bronchoscopic thermal vapor ablation (BTVA), biological lung volume reduction (BioLVR), and use of airway bypass stents (ABS). To date, several randomized controlled trials of these bronchoscopic therapies have been conducted in patients with emphysema, and bronchoscopic volume reduction with valve implants remains the best approach thus far. Recent studies indicate that BLVR may be of great value in improving lung function, exercise capacity, and quality of life and that BLVR has the potential to replace conventional surgery for patients with severe emphysema. Optimal patient selection and the proper selection of the BLVR technique in accordance with patient characteristics are crucial to the success of BLVR. More multicenter, prospective, randomized controlled trials need to be conducted in the future to optimize the current selection strategy and evaluate the safety, efficiency, and long-term benefit of BLVR techniques.
Various histones, including testis-specific histones, exist during spermatogenesis and some of them have been reported to play a key role in chromatin remodeling. Mass spectrometry (MS)-based characterization has become the important step to understand histone structures. Although individual histones or partial histone variant groups have been characterized, the comprehensive analysis of histone variants has not yet been conducted in the mouse testis. Here, we present the comprehensive separation and characterization of histone variants from mouse testes by a top-down approach using MS. Histone variants were successfully separated on a reversed phase column using high performance liquid chromatography (HPLC) with an ion-pairing reagent. Increasing concentrations of testis-specific histones were observed in the mouse testis and some somatic histones increased in the epididymis. Specifically, the increase of mass abundance in H3.2 in the epididymis was inversely proportional to the decrease in H3t in the testis, which was approximately 80%. The top-down characterization of intact histone variants in the mouse testis was performed using LC-MS/MS. The masses of separated histone variants and their expected post-translation modifications were calculated by performing deconvolution with information taken from the database. TH2A, TH2B and H3t were characterized by MS/MS fragmentation. Our approach provides comprehensive knowledge for identification of histone variants in the mouse testis that will contribute to the structural and functional research of histone variants during spermatogenesis.
Inorganic polyphosphate [Poly(P)] induces differentiation of osteoblastic cells. In this study, matrix metalloproteinase (MMP)-13 small interfering RNA (siRNA) was transfected into human adipose tissue-derived mesenchymal stem cells (hAT-MSC) to investigate whether MMP-13 activity induced by Poly(P) is associated with osteogenic differentiation. Real-time quantitative polymerase chain reaction, Western blotting, and an MMP-13 activity assay were used in this study. Poly(P) enhanced expression of mature osteoblast markers, such as osteocalcin (BGLAP) and osteopontin (SPP1), osterix (OSX), and bone sialoprotein (BSP), and increased alkaline phosphatase (ALP) activity and calcification capacity in hAT-MSCs. These cells also developed an osteogenic phenotype with increased expression of Poly(P)-induced expression of MMP-13 mRNA and protein, and increased MMP-13 activity. MMP-13 siRNA potently suppressed the expression of osteogenic biomarkers BGLAP, SPP1, OSX, BSP, and ALP, and blocked osteogenic calcification. Taken together, Poly(P)-induced MMP-13 regulates differentiation of osteogenic cells from hAT-MSCs.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and other cognitive functions and presents an increasing clinical challenge in terms of diagnosis and treatment. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and proliferation. In the present study, the mRNA and protein expression level of BDNF was detected in serum, and cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), dementia of Alzheimer's type (DAT), and hippocampus in APP/PS1 mice. A significant decrease of BDNF mRNA and protein expression was observed in serum and CSF of patients and hippocampus in APP/PS1 mice compared with the corresponding controls. miR-613, which is predicted to target the 3'-UTR of BDNF, was also detected in patients and the mouse model. Opposite to the alteration of BDNF, miR-613 expression in serum, CSF and hippocampus were obviously increased compared to the controls. In conclusion, these findings showed that miR-613 may function in the development of AD and may provide new insights in diagnosis and treatment of AD.
Hepatocellular carcinoma (HCC) is the most common neoplasms. Little progress has been made in the diagnosis and treatment of HCC and its prognosis remains poor. Studies have increasingly found that long non-coding RNA (lncRNA) is involved in the regulation of the occurrence and development of HCC. To investigate the diagnostic and prognostic value of lncRNA in HCC, the current study examined 25 lncRNAs with differing levels of expression (according to the fold change) in microarray databases. Expression of LINC RP1130-1 was found to be markedly down-regulated in 51 HCC tissues compared to matching adjacent non-tumor liver tissues. The pattern of expression and clinical significance of LINC RP1130-1 were examined in HCC. The area under the receiver operating characteristic (ROC) curve was 0.74 for LINC RP1130-1. The expression of LINC RP1130-1 was associated with clinical stage, the number of tumors, portal vein tumor thrombus (PVTT), and microvascular invasion (MVI). More importantly, patients with a low level of LINC RP1130-1 expression had a shorter recurrence-free survival (RFS) (n = 51, p < 0.05) than those with a high level of LINC RP1130-1 expression. Taken together, these findings indicate that a low level of LINC RP1130-1 expression in patients with HCC may be a powerful tumor biomarker, with potential clinical use in diagnosing and predicting the prognosis for patients with HCC.
The rhizome of Dioscorea bulbifera Linn, traditionally used to treat thyroid disease and cancer in China, is reported to induce serious liver injury during clinical practice. Diosbulbin B (DB), a diterpene lactone, has been found to be the main toxic compound in D. bulbifera. The present study aims to investigate the protection of ferulic acid (FA) against DB-induced acute liver injury and its engaged mechanism. Mice were orally administered FA (20, 40, 80 mg/kg) once daily for 6 consecutive days; and then orally given DB (250 mg/kg) on the last day. Daily FA (40, 80 mg/kg) decreased DB (250 mg/kg)-induced increase in serum levels of alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP). Histological evaluation showed that FA (80 mg/kg) ameliorated DB-induced hepatocellular degeneration and lymphocyte infiltration. Results of terminal dUTP nick-end labeling (TUNEL) staining assay showed that FA (80 mg/kg) decreased the DB-increased number of apoptotic hepatocytes. FA (40, 80 mg/kg) reduced DB-increased liver malondialdehyde (MDA) amount. FA (40, 80 mg/kg) decreased DB-increased serum levels of tumor necrosis factor alpha (TNF-α) and interferon-γ (IFN-γ), and liver myeloperoxidase (MPO) activity. FA (80 mg/kg) reversed the DB-induced decrease in expression of inhibitor of kappa B (IκB) and the increase in nuclear translocation of the p65 subunit of nuclear factor kappa B (NFκBp65). Taken together, our results demonstrate that FA prevents DB-induced acute liver injury via inhibiting intrahepatic inflammation and liver apoptosis.
Multidrug resistance (MDR) represents a clinical obstacle to cancer chemotherapy since it causes cancer recurrence and metastasis. Acetyl-11-keto-β-boswellic acid (AKBA), an active ingredient derived from the plant Boswellia serrata, has been found to inhibit the growth of a wide variety of tumor cells, including glioma, colorectal cancer, leukemia, human melanoma, hepatocellular carcinoma, and prostate cancer cells. However, the actions of AKBA in multidrug-resistant cancer cells have not been fully elucidated. The current study examined the reversal of MDR by AKBA in a human ileocecal adenocarcinoma cell line with vincristine-induced resistance, HCT-8/VCR. A 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay indicated that cytotoxicity increased drastically and the IC50 of VCR in HCT-8/VCR cells decreased in the presence of AKBA. AKBA had a maximum "fold reversal" of MDR (FR) of 9.19-fold. In addition, HCT-8/VCR cells treated with AKBA and VCR exhibited a higher percentage of apoptotic tumor cells according to flow cytometry. The reversal of MDR by AKBA was evident in an intracellular increase in Rhodamine (Rh123), indicating that the activity of P-glycoprotein (P-gp) was blocked. Furthermore, AKBA inhibited the expression of P-gp and decreased levels of expression of multidrug resistance gene 1 in HCT-8/VCR cells. The current results indicated that AKBA might be a potential agent to reverse MDR in human ileocecal adenocarcinoma.
Osteoimmunology is a new discipline that focuses on the interaction between the bones and the immune system. Immune cells play an important role in bone metabolism. The aim of this study was to illustrate the effect of Bu-Shen-Ning-Xin Decoction (BSNXD) on lymphocytes in the spleen and bone marrow to explore the potential role on the bone. C57BL/6 mice were divided into four groups: sham, ovariectomized (OVX), OVX+BSNXD, and OVX+ estrogen. The sham and OVX groups were treated with saline, the OVX+BSNXD group was treated with BSNXD, and the OVX+ estrogen group was treated with estrogen. After mice were sacrificed, the spleens and bones were collected, and the lymphocytes in the spleen and bone marrow were analyzed. We found that BSNXD lessened the extent of the increase of CD4+ and bone marrow. In contrast, these numbers were both increased in the OVX group. BSNXD had no influence on the percentage of γδ T cells. However, it increased the proportion of NK cells in the spleen and bone marrow. BSNXD lessened the extent of the increase of monocytes by ovariectomy. In vitro experiment, we found Tregs can decrease osteoclastogenesis when co-cultured with osteoclast precursor cells. This study suggests that BSNXD changes the immune environment and immune cells have a role in bone metabolism in OVX mice.
The aim of this study was to corroborate the hypothesis that Tao-Hong-Si-Wu Decoction (THSWD) affects steroid-induced avascular necrosis of the femoral head (SANFH) by regulating the hypoxia-inducible factor 1α (HIF-1α) pathway. Forty-eight New Zealand rabbits were randomly divided into a normal control group (NC group), a model group (SANFH group), a THSWD group, and a dimethyloxalylglycine group (DMOG group). Rabbits in the SANFH group were injected with both horse serum and methylprednisolone. Rabbits in the THSWD group were gavaged with THSWD in addition to receiving the same treatment as the SANFH group. Rabbits in the DMOG group were injected with extra DMOG in conjunction with the same treatment as the SANFH group. Rabbits in the NC group received the same amount of normal saline. Eight weeks after steroid treatment, the femoral heads of rabbits were removed to examine HIF-1α, vascular endothelial growth factor (VEGF), caspase-3, and bcl-2. Results indicated that THSWD significantly promoted the expression of HIF-1α and VEGF in the femoral head tissue of rabbits and markedly inhibit the apoptosis of osteocytes, chondrocytes, and bone marrow cells. In addition, THSWD suppressed caspase-3 expression and induced bcl-2 expression in femoral head tissues. In conclusion, THSWD can suppress SANFH by regulating the HIF-1α pathway and cell apoptosis.
HIV/AIDS is a major public health and social problem worldwide, and non-governmental organizations (NGOs) have played an irreplaceable role in HIV/AIDS prevention and control. At the present time, however, NGOs have not fully participated in HIV/AIDS prevention and control in China. As an emerging focus on international academic inquiry, social capital can provide a new perspective from which to promote the growth of NGOs. The Joint United Nations Program on HIV/AIDS (UNAIDS) recommends creating regional policies tailored to multiple and varying epidemics of HIV/AIDS. In order to provide evidence to policymakers, this paper described the basic information on NGOs and their shortage of social capital. This paper also compared the actual NGOs to "government-organized non-governmental organizations" (GONGOs). Results indicated that i) Chinese NGOs working on HIV/AIDS are short of funding and core members. GONGOs received more funding, had more core members, and built more capacity building than actual NGOs; ii) Almost half of the NGOs had a low level of trust and lacked a shared vision, networks, and support. The staff of GONGOs received more support from their organization than the staff of actual NGOs. Existing intra-organizational social capital among the staff of NGOs should be increased. Capacity building and policymaking should differentiate between actual NGOs and GONGOs. The relationship between social capital and organizational performance is a topic for further study.