Effects of squalene on expression of LDLR in HepG2 cells and its mechanism北大核心CSCD

Aim To investigate the effect of squalene on LDLR expression in HepG2 cells and its mechanism of down-regulated cholesterol. Methods The proliferation of HepG2 cells exposed to squalene at different concentrations was measured by MTT assay. The effect of squalene on the expression of LDLR in HepG2 cells was measured by flow cytometry and fluorescence mi-croscopy. The effect of different concentrations of squalene on the interaction between SCAP and Insig2, two key protein molecules of SREBP pathway, was assayed by FRET technology. Results MTT results showed that squalene had inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner. Flow cytometry and fluorescence microscopy results showed that squalene enhanced LDLR expression in HepG2 cells compared with the control group. The results of FRET technology revealed that compared with model control group, the YFP fluorescence value in Squalene group dramatically declined, and the YFP fluorescence value of each drug group decreased with the range of 5-25 |xmol L1 squalene concentration. Conclusions Squalene may promote the expression of LDLR in HepG2 cells through inhibiting the interaction between SCAP and Insig2 proteins in SREBP pathway, which may confirm that squalene is a potential novel drug for the down-regulation of cholesterol level. © 2018 Publication Centre of Anhui Medical University. All rights reserved.     

Injection Drug Use Trajectories among Migrant Populations: A Narrative Review

Background: Dual epidemics of injection drug use and blood-borne disease, characterized as “syndemics,” are present in a range of settings. Behaviors that drive such syndemics are particularly prevalent among mobile drug-using populations, for whom cross-border migration may pose additional risks. Objectives: This narrative review aims to characterize the risk factors for injection drug use initiation associated with migration, employing a risk environment framework and focusing on the San Diego–Tijuana border region as the most dynamic example of these phenomena. Methods: Based on previous literature, we divide migration streams into three classes: intra-urban, internal, and international. We synthesized existing literature on migration and drug use to characterize how mobility and migration drive the initiation of injection drug use, as well as the transmission of hepatitis and HIV, and to delineate how these might be addressed through public health intervention. Results: Population mixing between migrants and receiving communities and the consequent transmission of social norms about injection drug use create risk environments for injection drug use initiation. These risk environments have been characterized as a result of local policy environments, injection drug use norms in receiving communities, migration-related stressors, social dislocation, and infringement on the rights of undocumented migrants. Conclusion: Policies that exacerbate risk environments for migrants may inadvertently contribute to the expansion of epidemics of injection-driven blood-borne disease. Successful interventions that address emerging syndemics in border regions may therefore need to be tailored to migrant populations and distinguish between the vulnerabilities experienced by different migration classes and border settings.     

Efficacy of metformin in the management of periodontitis: A systematic review and meta-analysis

Periodontitis is characterized by inflammation of the periodontium and leads to loss of teeth if untreated. Although a number of surgical and pharmacological options are available for the management of periodontitis, it still affects a large proportion of population. Recently, metformin (MF), an oral hypoglycemic, has been used to treat periodontitis. The aim of this review is to systematically evaluate the efficacy of MF in the treatment of periodontitis. An electronic search was carried out using the keywords ‘metformin’, ‘periodontal’ and ‘periodontitis’ via the PubMed/Medline, ISI Web of Science and Google Scholar databases for relevant articles published from 1949 to 2016. The addressed focused question was: ‘Is metformin effective in reducing bone loss in periodontitis? Critical review and meta-analysis were conducted of the results obtained in the selected studies. Following the removal of the duplicate results, the primary search resulted in 17 articles and seven articles were excluded based on title and abstract. Hence, 10 articles were read completely for eligibility. After exclusion of four irrelevant studies, six articles were included. The topical application of MF resulted in improved histological, clinical and radiographic outcomes. Additionally, results from the meta-analysis indicated that application of metformin improved the clinical and radiographic outcomes of scaling and root-planing, but at the same time heterogeneity was evident among the results. However, because of a lack of histological and bacterial studies, in addition to short follow-up periods and risk of bias, the long-term efficacy of MF in the treatment of bony defects is not yet ascertained. Further studies are needed to envisage the long-term efficacy of MF in the management of periodontitis.     

Bauhinia forficata in the treatment of diabetes mellitus: a patent review

Introduction: Diabetes Mellitus has been considered an epidemic by the World Health Organization, with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as phytotherapic, and one of the most used plants is Bauhinia forficata.

Areas covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI.

Expert opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed. Although there are some phytotherapy products containing this medicinal plant which has hypoglycemic effect here is still a need for the development of more products based on natural resources, for the treatment of this pathology, without side effects and with other benefits, to assist in the glycemia control in diabetic patients, and to improve their quality of life.     

Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs

Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs.     

Phase II investigational oral drugs for the treatment of radio/chemotherapy induced oral mucositis

Introduction: Oral mucositis is a significant unmet clinical need for many cancer patients. The biological complexity of mucositis’ pathogenesis provides a number of mechanistic targets suitable as pharmacologic targets. The diversity of targets has stimulated drug development in search of an effective intervention. In this paper, we review a range of agents that are currently being evaluated.

Areas covered: Drugs for management of oral mucositis vary in formulation, route of administration and biological target. Most propose to interrupt the initiation of injury by suppressing activation of the innate immune response or countering oxidative stress, or minimizing downstream inflammatory responses. Overwhelmingly, the population most studied is patients being treated with concomitant chemoradiation for cancers of the head and neck as this is the cohort that most consistently suffers severe mucositis for long periods of time. The Phase 2 pipeline is robust. Preliminary data reported for a number of agents is optimistic. Genomics may be important in interpreting and comparing responses to agents across widely demographically diverse populations.

Expert opinion: Oral mucositis remains a significant toxicity for patients undergoing cancer treatment. Incremental reports of successes have been noted for a number of targeted agents.     

Mechanism of acid production and secretion by osteoclasts]

Osteoclasts are primary cells responsible for bone resorption. The most characteristic feature of osteoclasts is the presence of ruffled borders and clear zones. The resorbing area under the ruffled border of osteoclasts is acidic, which favors dissolution of bone mineral. In bone-resorbing osteoclasts, hydrogen ions are provided by carbonic anhydrase II, which catalyzes the hydration of CO2 to H2CO3. Recently, it has been shown that the proton pump of the vacuolar H(+)-ATPase type exists in the ruffled border membranes of osteoclasts. Secretion of hydrogen ions by osteoclasts generates an equal amount of cytoplasmic base equivalents, principally as HCO3-. Osteoclasts have a chloride/bicarbonate exchanger, which normalizes the intracellular pH when osteoclasts actively resorb bone. In this paper, we review the mechanism of the acid secretion by osteoclasts.