Systematic review on medicinal plants used for the treatment of Giardia infection

BackgroundHowever, broad adoption of herbal remedies for giardiasis is at present hampered by uncertain findings of investigation not always sufficiently powered. This study was aimed at systematically reviewing the existing literature in herbal medicines to treat giardiasis.MethodsThis review was carried out 06- PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. The search was performed in five databases which are Scopus, PubMed, Web of Science, EMBASE, and Google Scholar without time limitation for all published articles (in vitro, in vivo, and clinical studies). The searched words and terms were: “Giardia”, “giardiasis”, “extract”, “essential oil”, “herbal medicines”, “anti-Giardia”, “In vitro”, “In vivo”, “clinical trial” etc.ResultsOut of 1585 papers, 40 papers including 28 in vitro (70.0%), 7 in vivo (17.5%), 2 in vitro/ in vivo (5.0%), and 3 clinical trials (7.5%) up to 2020, met the inclusion criteria for discussion in this systematic review. The most widely used medicinal plants against Giardia infection belong to the family Lamiaceae (30.0%) followed by Asteraceae (13.5%), Apiaceae (10.5%). The most common parts used in the studies were aerial parts (45.0%) followed by leaves (27.4%) and seeds (7.5%). The aqueous extract (30.0%), essential oil (25.4%) and hydroalcholic and methanolic (10.5%) were considered as the desired approaches of herbal extraction, respectively.ConclusionThe current review showed that the plant-based anti-Giardia agents are very promising as an alternative and complementary resource for treating giardiasis since had low significant toxicity. However, more studies are required to elucidate this conclusion, especially in clinical systems.     

Stereoselective regulations of P-glycoprotein by ginsenoside Rh2 epimers and the potential mechanisms from the view of pharmacokinetics

Chirality is an interesting topic and it is meaningful to explore the interactions between chiral small molecules and stereoselective biomacromolecules, with pre-clinical and clinical significances. We have previously demonstrated that 20(S)-ginsenoside Rh2 is an effective P-glycoprotein (P-gp) inhibitor in vitro and in vivo. Considering the stereochemistry of ginsenoside Rh2, in our present study, the regulatory effects of 20(R)-Rh2 on P-gp were assayed in vivo, and the differential regulations of P-gp by ginsenoside Rh2 epimers in vivo were compared and studied. Results showed that 20(S)-Rh2 enhanced the oral absorption of digoxin in rats in a dose-dependent manner; 20(R)-Rh2 at low dosage increased the oral absorption of digoxin, but this effect diminished with elevated dosage of 20(R)-Rh2. Further studies indicated stereoselective pharmacokinetic profiles and intestinal biotransformations of Rh2 epimers. In vitro studies showed that Rh2 epimers and their corresponding deglycosylation metabolites protopanaxadiol (Ppd) epimers all exhibited stereoselective regulations of P-gp. In conclusion, in view of the in vitro and in vivo dispositions of Rh2 and the regulations of P-gp by Rh2 and Ppd, it is suggested that the P-gp regulatory effect of Rh2 in vivo actually is a double actions of both Rh2 and Ppd, and the net effect is determined by the relative balance between Rh2 and Ppd with the same configuration. Our study provides new evidence of the chiral characteristics of P-gp, and is helpful to elucidate the stereoselective P-gp regulation mechanisms of ginsenoside Rh2 epimers in vivo from a pharmacokinetic view.     

Basic fibroblast growth factor enhances the osteogenic differentiation induced by bone morphogenetic protein-6 in vitro and in vivo

Some members of the bone morphogenetic protein subfamily (BMP-2 and -7) are currently used in orthopedic surgery for several applications. Although their use is considered safe at short term, the high doses of growth factors needed make these treatments expensive and their safety uncertain at long term. BMP-6 has been much less studied than BMP-2 and -7, but some authors suggest that this BMP might have a stronger osteogenic activity than the previously mentioned. Having in mind that angiogenesis plays a well-known role during bone formation, the aim of this work was to study the effect of combining BMP-6 with bFGF on both the growth and differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs), as well as on in vivo osteogenesis. We demonstrate that a low dose of bFGF enhances the osteogenic differentiation of MSCs induced by BMP-6 in vitro. Furthermore, we also demonstrate that bone formation in vivo induced by BMP-6 can be accelerated and enhanced by adding a low dose of bFGF, what might suggest a synergic effect between these growth factors on in vivo osteogenesis.     

“Saddle-shaped” dose-survival effect,is it a general and valuable phenomenon in microbes in response to heavy ion beam irradiation?

We aimed to verify the “saddle-shaped” dose-survival effect of microbes in response to heavy ion beam irradiation (HI), and further determine the radiation parameter that affects saddle shape formation, and the relationship between the saddle region and the positive mutation rate. A bibliometric analysis was performed based on literature containing the dose-survival effect of microbes in response to HI, from which the data on the particle energies, ionic types, irradiated microbes, survival curves, and maximum positive mutation rates were assembled. Articles reporting a “saddle-shaped” survival curve accounted for 64% of the total relevant articles and possessed a high cited frequency. The predominant articles, authors, and institutions that reported the dose-survival effect of microbes in response to HI proposed the “saddle-shaped” survival curve. It was customarily low-energy (but not moderate- or high-energy) HI that induced the “saddle-shaped” dose-survival effect. In addition, the “saddle-shaped” dose-survival effect was general among ~ 30-genera microbes. More importantly, most of the saddle regions contained the survival fractions within 10–30%, which are customarily used to screen mutants due to a high positive mutation rate. Further, 87% of the maximum positive mutation rates were associated with the saddle region, and 58% were located in the peak of the saddle region. “Saddle-shaped” dose-survival effect is a reliable and general phenomenon among varieties of microbes customarily in response to low-energy HI. Meanwhile, saddle region is always accompanied with high positive mutation rates. Thus, this study will aid in microbial mutation breeding practices.

     

Expression of bone morphogenetic proteins, matrix metalloproteinases and inhibitors of matrix metalloproteinases in lung cancers and their prognostic significance

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are one of the molecules that have become a topic of great interest among scientists studying lung cancers. There is a distinct tendency toward higher expression of selected MMP and TIMP in tumor lung tissue. Furthermore, there is a significant correlation between high expression of TIMP-1 or MMP-2 in lung cancer and shortened survival and between high expression of TIMP-1 or MMP-7 in lung cancer and higher stage of disease. There have been only a few articles about the role of bone morphogenetic proteins (BMP) in lung cancer pathogenesis published so far in which BMP-2 or BMP-4 were overexpressed. It was also shown that BMP-2 stimulates tumor growth while BMP-4 inhibits it. This article is mainly concentrated on the expression of MMP, TIMP and BMP in lung cancers, but also it shows the significance of these proteins.     

Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations

The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind “colors” of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin-3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology.     

Potential role of bone morphogenetic protein-15 in zebrafish follicle development and oocyte maturation

Bone morphogenetic protein (BMP)-15 is a member of the transforming growth factor beta (TGF-beta) superfamily and is closely related to growth and differentiation factor (GDF)-9, both structurally and functionally. In mammals, BMP-15 is predominantly produced by oocytes and exerts important regulatory functions within the ovary, such as promoting early folliculogenesis, preventing premature luteinization and enhancing cumulus cell expansion. The role of BMP-15 in mammalian ovary differs between monoovulatory and polyovulatory species. Recent studies in zebrafish have provided initial evidence that BMP-15 is also an important regulator of ovarian functions. BMP-15 is produced by the zebrafish ovary throughout follicle development and maturation. In vitro studies using zebrafish follicles have revealed that incubation with recombinant human BMP-15 or over-expression of BMP-15 in oocytes results in an inhibition of gonadotropin- and maturation inducing hormone (MIH)-induced oocyte maturation. Conversely, immnunoneutralization with BMP-15 antiserum or silencing of BMP-15 expression using morpholino antisense oligonueclotides enhances oocyte maturation. A key step in BMP-15 action is the sensitivity of follicles to MIH. In vivo injection of BMP-15 antiserum causes a significant decrease in maturation-incompetent (insensitive to MIH) small early growth phase follicles and a concomitant increase in mature follicles. These findings support a role in BMP-15 in preventing precocious oocyte maturation in zebrafish. We propose that the suppression of premature oocyte maturation by BMP-15 may be important to maintain oocyte quality and subsequent ovulation and fertilization.     

Opposing effects by glucocorticoid and bone morphogenetic protein-2 in fetal rat bone cell cultures

Glucocorticoid in excess produces bone loss in vivo. Consistent with this, it reduces the stimulatory effect of transforming growth factor β (TGF-β) on collagen synthesis in osteoblast-enriched cultures in vitro, where it also suppresses TGF-β binding to its type I receptors. Analogous studies with bone morphogenetic protein-2 (BMP-2) show directly opposite results. These findings prompted us to assess the effect of glucocorticoid on BMP-2 activity in cultured bone cells, and whether either agent had a dominant influence on TGF-β binding or function. BMP-2 activity was retained in part in osteoblast-enriched cultures pre-treated or co-treated with cortisol, and was fully evident when glucocorticoid exposure followed BMP-2 treatment. In addition, BMP-2 suppressed the effects of cortisol on TGF-β activity, on TGF-β binding, and on gene promoter activity directed by a glucocorticoid sensitive transfection construct. While BMP-2 also alters the function of less-differentiated bone cells, it only minimally prevented cortisol activity in these cultures. Our studies indicate that BMP-2 can oppose certain effects by cortisol on differentiated osteoblasts, and may reveal useful ways to diminish glucocorticoid-dependent bone wasting. J. Cell. Biochem. 67:528–540, 1997. © 1997 Wiley-Liss, Inc.     

Production of an antibody-like factor in the sea star Asterias rubens: Role of the gastric haemal tufts

Cells from the axial organ (AO) of sea stars stimulated “in vivo” with TNP coupled to polyacrylamide beads and subsequently cultured “in vitro” were able to produce an antibody-like factor which induced the lysis of mammalian red cells sensitized with TNP. Three types of cells at least are involved in the production of the antibody-like factor. The addition of 2-mercapto-ethanol to the cultures including these 3 populations was essential but what is a novelty is the fact that cells from the gastric haemal tufts (G.H.T.), probably phagocytes, are able to replace it. Otherwise G.H.T. contain cells playing the role of nylon wool- non adherent AO cells or T like cells.     

Estimating Extracellular Concentrations of Dopamine and 3,4-Dihydroxyphenylacetic Acid in Nucleus Accumbens and Striatum Using Microdialysis: Relationships Between In Vitro and In Vivo Recoveries

Abstract: It is common practice in microdialysis studies for probes to be “calibrated” in artificial CSF and in vitro recoveries determined for all substances to be measured in vivo. Dialysate concentrations of such substances are then “corrected” for in vitro recoveries to provide “estimates” of extracellular concentrations. At least for dopamine, in vitro and in vivo recoveries are significantly different and, therefore, an estimate of extracellular dopamine based on correction for in vitro recovery is likely to be erroneous. Generally, however, the relative relationships of such estimates among animals are of interest rather than the “true” extracellular values. Such relationships would be valid to the extent that estimated values are correlated with or predictive of true values. Using the “no net flux” procedure, the present study sought to determine, for both dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC), whether in vitro and in vivo recoveries would correlate with each other as well as whether respective estimated and true (no net flux) values of these substances would correlate with each other. Probes (3 mm; BAS/CMed MF-5393), previously calibrated, were lowered into both the nucleus accumbens and striatum of freely moving rats the day before sample collection was begun. In vitro and in vivo recoveries were not significantly correlated (r= 0.1–0.3), for either dopamine or DOPAC. For both dopamine and DOPAC, however, there were significant correlations (r= 0.7–0.8) between estimated and true values. Surprisingly, when using these commercial probes, absolute dialysate levels for both substances were even better correlated (r = 0.9–0.95) with true values. This suggests that, with these probes, a direct comparison of dialysate concentrations can be used to determine relative changes in basal extracellular levels of dopamine and DOPAC when it is not practical to do no net flux studies (e.g., because of the time required to characterize a drug effect). The use of in vitro calibrations adjusts the values closer to the true values but also adds noise to each value and therefore should be avoided.     

Honey and diabetes mellitus: Obstacles and challenges – Road to be repaired

Background and objectiveSince ancient times, honey has been used due to its nutritional and therapeutic value. The role of honey has been acknowledged in the scientific literature however, its use has been controversially discussed and has not been well accepted in modern medicine especially for diabetic patients. This study aimed to investigate the role of honey in diabetic patients.MethodsIn this study, we identified 107 research articles from data based search engines including “PubMed”, “ISI-Web of Science”, “Embase” and “Google Scholar”. The research papers were selected by using the primary key-terms including “Honey”, “Honey bee” and “Diabetes Mellitus”. The research documents in which “Honey” and “Diabetes Mellitus” were debated are included. After screening, we reviewed 66 papers and finally we selected 35 studies which met the inclusion criteria and the remaining documents were excluded.ResultsThis study investigated the preclinical, clinical, human and animal model studies on honey and diabetes mellitus and found that honey decreases the fasting serum glucose, increases the sting C-peptide and 2-h postprandial C-peptide. Although, there is a dearth of data and literature also contrary discussed the use of honey in diabetic patients.ConclusionHoney decreases the fasting serum glucose, increases fasting C-peptide and 2-h postprandial C-peptide. Honey had low glycemic index and peak incremental index in diabetic patients. The use of honey in diabetic patients still has obstacles and challenges and needs more large sample sized, multi-center clinical controlled studies to reach better conclusions.     

Finding academic concerns of the Three Gorges Project based on a topic modeling approach

The Three Gorges Project (TGP) has gone into the overall completion acceptance stage in 2014. As the world's largest hydropower project, the TGP has attracted worldwide attention over the past few decades. Previous studies mainly focused on a single aspect, such as engineering technologies, social impacts and environmental impacts, of the TGP. However, a large-scale review gathering systematic data to find academic concerns about the TGP is missing. Topic model is a text mining approach for discovering latent topics in a collection of documents. In this article, an emerging topic modeling approach, Latent Dirichlet Allocation (LDA), was introduced to uncover the intellectual structure of the academic literature focusing on the TGP. A collection of 8280 Chinese research articles highly related to the TGP was established with a time frame ranging from 2001 to 2013, and an 18-topic model was used to describe the intellectual structure. Two novel bibliometric indicators, including topic proportion and topic trend, were constructed to describe the academic concerns of the TGP. Topic proportion analysis shows that post-construction issues, including the social and environmental impacts brought by the TGP, have attracted more attention than the construction issues. “Ecology”, “Reservoir Operation”, “Land Administration”, and “Water Pollution”, have become the dominant research topics regarding the TGP during these years. Meanwhile, “Construction Technology” and “Design”, have gradually lost scholars’ interest. The results show that the approach reported in this study can provide sound and credible conclusions of the major academic concerns for a hydropower project. The topic modeling approach is expected to be widely applied as a methodological strategy in future hydropower and other infrastructure project assessment.     

BMP-2 induces a profibrotic phenotype in adult renal progenitor cells through Nox4 activation

Adult renal progenitor cells (ARPCs) isolated from the human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling, and regeneration processes in several tissues. The aim of this study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidneys, and it was upregulated in vivo after delayed graft function (DGF) of renal transplantation, a condition of AKI. ARPCs expressed BMP receptors, suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced reactive oxygen species (ROS) production, NADPH oxidase activity, and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at the tubular level after DGF. BMP-2 incubation induced α-smooth muscle actin (SMA), collagen I, and fibronectin protein expression in ARPCs. Moreover, α-SMA colocalized with CD133 in vivo after DGF. The oxidative stimulus (H(2)O(2)) induced α-SMA expression in ARPCs, while the antioxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that 1) ARPCs express BMP-2, 2) this expression is increased in a model of AKI; 3) BMP-2 may induce the commitment of ARPCs toward a myofibroblastic phenotype in vitro and in vivo; and 4) this profibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.     

Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neurons Survival by Activation of the MEK/ERK/CREB Pathway

Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGC death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium–mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, suggesting that the canonical pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by BMP-6 is necessary for its neuroprotective effect, which involves inhibition of caspase activity and an increase in Bcl-2 protein levels. Other pathways involved in the regulation of CGC survival, such as the c-Jun terminal kinase and the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6. Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its inability to protect CGCs from low potassium–mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway plays a crucial role on CGC survival.     

Effects of physical activity and training programs on plasma homocysteine levels: a systematic review

Homocysteine is an amino acid produced in the liver that, when present in high concentrations, is thought to contribute to plaque formation and, consequently, increased risk of cardiovascular disease. However, daily physical activity and training programs may contribute to controlling atherosclerosis. Given that physical exercise induces changes in protein and amino acid metabolism, it is important to understand whether homocysteine levels are also affected by exercise and to determine possible underlying mechanisms. Moreover, regarding the possible characteristics of different training programs (intensity, duration, repetition, volume), it becomes prudent to determine which types of exercise reduce homocysteine levels. To these ends, a systematic review was conducted to examine the effects of daily physical activity and different training programs on homocysteine levels. EndNote^® was used to locate articles on the PubMed database from 2002 to 2013 with the keyword combinations “physical activity and homocysteine”, “training and homocysteine”, and/or “exercise and homocysteine”. After 34 studies were identified, correlative and comparative studies of homocysteine levels revealed lower levels in patients engaged in greater quantities of daily physical activity. Regarding the acute effects of exercise, all studies reported increased homocysteine levels. Concerning intervention studies with training programs, aerobic training programs used different methods and analyses that complicate making any conclusion, though resistance training programs induced decreased homocysteine levels. In conclusion, this review suggests that greater daily physical activity is associated with lower homocysteine levels and that exercise programs could positively affect homocysteine control.     

Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7

Bone morphogenetic proteins (BMPs) are well-established agents for inducing orthotopic and ectopic bone formation. However, their clinical usefulness as regenerative agents may be limited by a short in vivo half-life and low specific activity. BMP gene therapy is an alternative route for exploiting the bone-inductive activity of this class of molecules. To test the feasibility of this approach, we examined the osteogenic activity of AdCMV-BMP7, an adenovirus containing BMP7 cDNA under control of the CMV promoter that was constructed using Cre/lox recombination (Hardy et al. [1997] J. Virol. 71:1842-1849). Adenovirus vectors were shown to readily infect a wide variety of cell types in vitro including osteoblasts, fibroblasts, and myoblasts. COS7 cells transduced with AdCMV-BMP7 produced high levels of BMP-7 (approximately 0.5 microg/10(6) cells). Furthermore, transduction of C2C12 murine myoblast cells with AdCMVBMP-7 suppressed the muscle phenotype and induced in vitro osteoblast differentiation. To test its in vivo biological activity, AdCMV-BMP7 was mixed with a bovine bone-derived collagen carrier (10(8) plaque-forming units virus/site) and was implanted into mouse muscle and dermal pouches. In both cases, an ossicle containing cortical and trabecular bone and a clearly defined marrow cavity formed at the site of virus implantation within 4 weeks. These data demonstrate that AdCMV-BMP7 transduced cells produce biologically active BMP-7 both in vitro and in vivo and show that gene therapy by direct viral transduction using a virus/matrix implant may be a viable route for stimulating bone regeneration.