Top Journal Content
2013, 27(2): 85-102. doi: 10.7555/JBR.27.20120064
Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemothera-peutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and afford-able antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-at-tenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many labo-ratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune re-sponses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.
2014, 28(1): 1-17. doi: 10.7555/JBR.28.20130191
Atrial fibrillation is the most common arrhythmia affecting patients today. Disease prevalence is increasing at an alarming rate worldwide, and is associated with often catastrophic and costly consequences, including heart failure, syncope, dementia, and stroke. Therapies including anticoagulants, anti-arrhythmic medications, devices, and non-pharmacologic procedures in the last 30 years have improved patients' functionality with the disease. Nonetheless, it remains imperative that further research into AF epidemiology, genetics, detection, and treatments continues to push forward rapidly as the worldwide population ages dramatically over the next 20 years.
2011, 25(1): 63-70. doi: 10.1016/S1674-8301(11)60008-0
Biomarkers play an important role in the detection at an early stage of pancreatic cancer. The aim of the present study was to optimize the conditions of antibody arrays for detecting Hippocalcin-like 1 (HPCAL1), phosphati-dylethanolamine binding protein 1 (PEBP1), lectin galactoside-binding soluble 7 (LGALS7), and serpin peptidase inhibitor clade E member 2 (SERPINE2) as biomarkers for pancreatic cancer detection in a single assay and to investigate antibodies’ specificity and cross-reactivity. Capture antibodies against HPCAL1, PEBP1, LGALS7 and SERPINE2 were printed on nitrocellulose coated glass slides. HPCAL1, PEBP1, LGALS7 and SERPINE2 proteins with different concentrations were incubated with the capture antibodies at different temperatures for different time periods. Biotinylated detection antibodies recognizing a different epitope on the captured proteins and a secondary detection molecule (Streptavidin-PE) were used to detect fluorescent signals. The arrays showed the strongest signals when the concentration of the capture antibodies was at 500 μg/mL in PBST0.05 (PBS with 0.05% Tween-20), and the slides were incubated overnight at 4°C. The lowest protein concentration for detection was 2 ng/mL. Each antibody demonstrated high specificity to the corresponding antigen in detecting a mixture of 4 proteins without significant cross-reactivity. The fluorescence and biomarker concentration displayed a linear correlation. The antibody microarray system could be a useful tool for potential biomarker detection for pancreatic cancer.
Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies
2019, 33(4): 221-234. doi: 10.7555/JBR.32.20180087
Hepatic ischemia-reperfusion injury is a major cause of liver transplant failure, and is of increasing significance due to increased use of expanded criteria livers for transplantation. This review summarizes the mechanisms and protective strategies for hepatic ischemia-reperfusion injury in the context of liver transplantation. Pharmacological therapies, the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies. The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemia-reperfusion injury, and is an exciting and active area of research, which needs more study clinically.
Maternal risk factors for low birth weight for term births in a developed region in China: a hospital-based study of 55,633 pregnancies
2013, 27(1): 14-22. doi: 10.7555/JBR.27.20120046
Low birth weight (LBW) is an important risk factor for neonatal and infant mortality and morbidity in adults.. How-ever, no large scale study on the prevalence of LBW and related maternal risk factors in China has been published. To explore the effects of maternal factors on LBW for term birth in China, we conducted a hospital-based retrospective study of 55, 633 Chinese pregnancy cases between 2001 and 2008. Maternal sociodemographic data, history of infer-tility and contraceptive use were obtained. Their medical status and diseases during pre-pregnancy were examined by physical examination at the first antenatal care visit. Maternal medical status before childbirth and pregnancy outcomes, including body weight, infant gender, multiple pregnancy and congenital anomalies, were recorded. Univariate and multivariate logistic regression, and linear regression were used to investigate the relationship be-tween maternal factors and term LBW. The general incidence of term LBW was 1.70% in the developed area of China. After preliminary analysis using the univariate model, low primary education, anemia, hypertensive disor-ders, placental previa, oligohydramnios and premature rupture of membrane were predicted as independent factors of term LBW in the multivariate model. Furthermore, the decrease in annual frquencies of these risk factors were major causes of gradual decline in the incidence of LBW (from 2.43% in 2001 to 1.21% in 2008). The study dem-onstrated that among maternal factors, primary education, anemia and hypertensive disorders could contribute to LBW for term birth even in the most developed area of China.
Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats
2011, 25(6): 411-417. doi: 10.1016/S1674-8301(11)60054-7
Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the general population. It is es-timated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renopro-tection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (90 mg/kg) in neonatal rats and then these rats were treated with rosiglitazone (1.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light mi-croscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepir-ide is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-a signal-ing during the development of streptozotocin induced type 2 diabetic nephropathy.
2013, 27(1): 1-13. doi: 10.7555/JBR.27.20120077
Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu-lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab-olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.
2012, 26(3): 143-151. doi: 10.7555/JBR.26.20120027
Nanotechnology is gaining tremendous impetus due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Nanoparticles have been introduced as materials with good potential to be extensively used in biological and medical applications. Nanoparticles are clusters of atoms in the size range of 1-100 nm. Inorganic nanoparticles and their nano-composites are applied as good antibacterial agents. Due to the outbreak of infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance, pharmaceutical companies and researchers are searching for new antibacterial agents. The metallic nanoparticles are the most promising as they show good antibacterial properties due to their large surface area to volume ratios, which draw growing interest from researchers due to increasing microbial resistance against metal ions, antibiotics and the development of resistant strains. Metallic nanoparticles can be used as effective growth inhibitors in various microorganisms and thereby are applicable to diverse medical devices. Nanotechnology discloses the use of elemental nanoparticles as active antibacterial ingredient for dental materials. In dentistry, both restorative materials and oral bacteria are believed to be responsible for restoration failure. Secondary caries is found to be the main reason to restoration failure. Secondary caries is primarily caused by invasion of plaque bacteria (acid-producing bacteria) such as Streptococcus mutans and lactobacilli in the presence of fermentable carbohydrates. To make long-lasting restorations, antibacterial materials should be made. The potential of nanoparticles to control the formation of biofilms within the oral cavity is also coming under increasing scrutiny. Possible uses of nanoparticles as topically applied agents within dental materials and the application of nanoparticles in the control of oral infections are also reviewed.
Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats
2012, 26(3): 200-210. doi: 10.7555/JBR.26.20110054
Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
2013, 27(4): 254-271. doi: 10.7555/JBR.27.20130030
The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein MDM2. In human cancers, the TP53 gene is frequently mutated or deleted, or the wild-type p53 function is inhibited by high levels of MDM2, leading to downregulation of tumor suppressive p53 pathways. Thus, the inhibition of MDM2-p53 interaction presents an appealing therapeutic strategy for the treatment of cancer. However, recent studies have revealed the MDM2-p53 interaction to be more complex involving multiple levels of regulation by numerous cellular proteins and epigenetic mechanisms, making it imperative to reexamine this intricate interplay from a holistic viewpoint. This review aims to highlight the multifaceted network of molecules regulating the MDM2-p53 axis to better un-derstand the pathway and exploit it for anticancer therapy.
Leishmania donovani whole cell antigen delivered with adjuvants protects against visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops)
2012, 26(1): 8-16. doi: 10.1016/S1674-8301(12)60002-5
In a previous immunogenicity and efficacy study in mice, montanide ISA 720 (MISA) was indicated to be a better adjuvant than bacillus calmette guerin vaccine (BCG) for a Leishmania vaccine. In the present study, we report the safety, immunogenicity and efficacy of Leishmania donovani (L. donovani) sonicated antigen delivered with alum-BCG (AlBCG), MISA or monophosphoryl lipid A (MPLA) in vervet monkeys following intradermal inoculums. Vaccinated and control animals were challenged with virulent L. donovani parasites and the parasitic burden was determined. Only animals vaccinated with alum-BCG adversely reacted to the inoculum by produc-ing ulcerative erythematous skin indurations. Non-parametric ANOVA followed by a post test showed signifi-cantly higher IgG antibodies, and revealed the presence of lymphoproliferative and interferon gamma responses in both AlBCG+Ag and MISA+Ag as compared to the MPLA+Ag or other groups (P < 0.001). We conclude that L. donovani sonicated antigen containing MISA is safe and is associated with protective immune response against Leishmania donovani infection in the vervet monkey model.
2011, 25(6): 418-424. doi: 10.1016/S1674-8301(11)60055-9
We studied the fracture resistance of maxillary premolars restored with recent restorative materials. Fifty max-illary premolars were divided into five groups: Group 1 were unprepared teeth; Group 2 were teeth prepared with-out restoration; Group 3 were teeth restored with tetric ceram HB; Group 4 were teeth restored with InTen S; and Group 5 were teeth restored with Admira. The samples were tested using a universal testing machine. Peak loads at fracture were recorded. The teeth restored with Admira had the highest fracture resistance followed by those re-stored with InTen-S and tetric ceram HB. Prepared, unrestored teeth were the weakest group. There was a signifi-cant difference between the fracture resistance of intact teeth and the prepared, unrestored teeth. There was also a significant difference among the tested restorative materials. Teeth restored with Admira showed no significant difference when compared with the unprepared teeth. It was concluded that the teeth restored with Admira exhib-ited the highest fracture resistance.
2012, 26(3): 226-234. doi: 10.7555/JBR.26.20120023
In the current study, we sought to investigate whether lysed Enterococcus faecalis FK-23 (LFK), a heat-killed probiotic preparation, attenuated eosinophil influx into the upper airway and had immunomodulatory activity in a murine allergic rhinitis model. Eighteen BALB/c mice were divided into three groups; the ovalbumin (OVA)-sen-sitized/challenged group, which received saline orally for 6 weeks (OVA group), the OVA-sensitized/challenged group, which received LFK orally for 6 weeks (LFK-fed group), and the non-sensitized group, which received saline for 6 weeks (saline control group). Nasal rubbing and sneezing were monitored during the study. After the final challenge, interleukin (IL)-4, interferon (IFN)-γ, and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined, eosinophilic infiltrate into the upper airway was quantified, and splenic CD4+ CD25+ regulatory T cells (Tregs) were examined by flow cytometry. We found that nasal rubbing was sig-nificantly reduced in LFK-fed mice compared to the OVA group on d 27 and 35, and sneezing was significantly inhibited by LFK administration for 35 d. LFK-fed mice had significantly less eosinophil influx into the nasal mucosa than the OVA group. There were no significant differences between the LFK-fed group and OVA group in the serum and splenocyte culture supernatant levels of IL-4, IFN-γ, and OVA-specific IgE. Interestingly, the LFK-fed mice had a significantly greater percentage of splenic CD4+CD25+ Tregs than OVA group. Our results indicate that oral administration of LFK may alleviate nasal symptoms, reduce nasal eosinophilia, and increase the percentage of CD4+CD25+ Tregs in experimental allergic rhinitis.
2019, 33(4): 235-243. doi: 10.7555/JBR.32.20180018
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to remove the major antigens [Gal, Neu5Gc, and Sd(a)] present on pig cells and tissues. Triple gene (GGTA1, CMAH, and β4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
2012, 26(4): 278-287. doi: 10.7555/JBR.26.20120030
Spermatogenesis is a complex process of terminal differentiation by which mature sperms are generated, and it can be divided into three phases: mitosis, meiosis and spermiogenesis. In a previous study, we established a series of proteomic profiles for spermatogenesis to understand the regulation of male fertility and infertility. Here, we further investigated the localization and the role of flotillin-2 in spermiogenesis. Flotillin-2 expression was inves-tigated in the testis of male CD1 mice at various developmental stages of spermatogenesis by using Western blot-ting, immunohistochemistry and immunofluorescence. Flotillin-2 was knocked down in vivo in three-week-old male mice using intratesticular injection of small inhibitory RNA (siRNA), and sperm abnormalities were assessed three weeks later. Flotillin-2 was expressed at high levels in male germ cells during spermatogenesis. Flotillin-2 immunoreactivity was observed in pachytene spermatocytes as a strong dot-shaped signal and in round spermatids as a sickle-shaped distribution ahead of the acrosome. Immunofluorescence confirmed flotillin-2 was localized in front of the acrosome in round spermatids, indicating that flotillin-2 was localized to the Golgi apparatus. Knock-down of flotillin-2 in vivo led to a significant increase in head sperm abnormalities isolated from the cauda epidi-dymis, compared with control siRNA-injected testes. This study indicates that flotillin-2 is a novel Golgi-related protein involved in sperm acrosome biogenesis.
Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling
2019, 33(4): 250-257. doi: 10.7555/JBR.32.20180031
The prevalence of cardiovascular diseases (CVDs) is increasing at a rapid pace in developed countries, and CVDs are the leading cause of morbidity and mortality. Natural products and ethnomedicine have been shown to reduce the risk of CVDs. Schizonepeta (S.) tenuifolia is a medicinal plant widely used in China, Korea, and Japan and is known to exhibit anti-inflammatory, antioxidant, and immunomodulatory activities. We hypothesized that given herbal plant exhibit pharmacological activities against CVDs, we specifically explored its effects on platelet function. Platelet aggregation was evaluated using standard light transmission aggregometry. Intracellular calcium mobilization was assessed using Fura-2/AM, and granule secretion (ATP release) was measured in a luminometer. Fibrinogen binding to integrin αⅡbβ3, was assessed using flow cytometry. Phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules and activation of the protein kinase B (Akt) was assessed using Western blot assays. S. tenuifolia, extract potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αⅡbβ3. Moreover, all extracts significantly inhibited MAPK and Akt phosphorylation. S. tenuifolia extract inhibited platelet aggregation and granule secretion, and attenuated collagen mediated GPVI downstream signaling, indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function. We suggest that S. tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.
Role of remote sensing, geographic bioinformatics system and bioinformatics in kala-azar epidemiology
2011, 25(6): 373-384. doi: 10.1016/S1674-8301(11)60050-X
Visceral leishmaniasis or kala-azar is a potent parasitic infection causing death of thousands of people each year. Medicinal compounds currently available for the treatment of kala-azar have serious side effects and de-creased efficacy owing to the emergence of resistant strains. The type of immune reaction is also to be considered in patients infected with Leishmania donovani (L. donovani). For complete eradication of this disease, a high level modern research is currently being applied both at the molecular level as well as at the field level. The computa-tional approaches like remote sensing, geographic information system (GIS) and bioinformatics are the key re-sources for the detection and distribution of vectors, patterns, ecological and environmental factors and genomic and proteomic analysis. Novel approaches like GIS and bioinformatics have been more appropriately utilized in determining the cause of visearal leishmaniasis and in designing strategies for preventing the disease from spread-ing from one region to another.
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage
2014, 28(3): 213-221. doi: 10.7555/JBR.28.20130105
Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization. Autophagy func?tions in bulk degradation of cellular components, has been recognized recently as an important mechanism for cell survive under endoplasmic reticulum (ER) stress. We previously found that engagement of the class A scavenger receptor (SR-A) triggered JNK-dependent apoptosis in ER-stressed macrophages. However, the pro-apoptosis mechanisms mediated by SR-A are not fully understood. We therefore sought to see if SR-A mediated apoptosis was associated with the autophagy in macrophages. In this study, we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates (LC3-II) formation as well as the number of autophago?somes under ER stress. The inhibition of LC3-II formation was paralleled by activation of mTOR pathways, and inhibition of mTOR allowed LC3-II induction in macrophages treated with thapsigargin plus fucoidan. Further?more, apoptosis induced by fucoidan was prevented under ER stress by the inhibitor of mTOR treatment. We propose that fucoidan, a SR-A agonist, may contribute to macrophages apoptosis during ER stress by inhibition of autophagy.
2014, 28(5): 388-395. doi: 10.7555/JBR.28.20140015
Astrocyte elevated gene-1 (AEG-1) is associated with tumor genesis and progression in a variety of human cancers. This study aimed to explore the significance of AEG-1 in glioma and investigate whether it correlated with radioresistance of glioma cells. Immunohistochemical staining showed that the intensity of AEG-1, CD133 and PPP6c protein expression in glioma tissues increased significantly, mainly in the cytoplasm. The expression rate of AEG-1, CD133 and PPP6c were 85.9% (67/78), 60.3% (47/78) and 65.8% (51/78), respectively. AEG-1 expression was correlated with age (r50.227, P50.045), clinical stage (r50.491, P,0.001) and clinical grade (r50.450, P,0.001). No correlation was found between AEG-1 expression and other clinicopathologic parameters (P.0.05). The expression of AEG-1 was positively correlated with the expression of CD133 (r50.240, P 5 0.035) and PPP6c (r5 0.250, P 5 0.027). In addition, retrieved data on TCGA implied co-occurrence of genomic alterations of AEG-1 and PPP6c in glioblastoma. Our findings indicate that AEG-1 is positively correlated with CD133 and AEG-1 expression. It may play an important role in the progression of glioma and may serve as potential novel marker of chemoresistance and radioresistance.