In vivo assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 271-271
Author(s):  
Amr Ammar ◽  
Mohamed Hessein ◽  
Emma Guns ◽  
Mei Chin ◽  
Abul Bashar Helaluddin ◽  
...  

271 Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti-thrombotic agents, cancer metastasis inhibitors and anti-microbials Currently, leech therapy is established as an important tool in microsurgery and reconstructive operations having demonstrated superior clinical outcomes for the optimal salvage of grafted tissues. Methods: In the current study, we have determined the in vivo efficacy of LSE from (Huridinaria manillensis) on castration resistant LNCaP xenograft mouse model. Mice were divided into three groups of six, mice were subcutaneously injected with either LSE (5 mg/kg), docetaxel (10 mg/kg), or vehicle once a week. PSA and tumor volume were measured weekly. After four weeks of treatment, mice were euthanized, tumors and organs were collected for transcriptome and immunohistochemical (IHC) analysis. Results: There was a significant decrease in the tumor volume and PSA with either docetaxel (10mg/kg) or LSE (5 mg/kg) treated groups compared to the control. While there was no significant difference between the anti-tumor activity of docetaxel (10mg/kg) and LSE (5 mg/kg). IHC showed significant increase in caspase-3 and significant decrease in Ki-67 and PCNA expression in the LSE treated mice compared to the control group. Interestingly, transcriptome analysis of tumor samples showed that LSE modulated cytokine production, monocyte adhesion, steroidogenesis, and P38 MAPK signaling pathways. Conclusions: LSE has significant anti-tumor activity in LNCaP tumor xenograft models with no apparent side effects. This can be attributed, at least partly, to its inhibition of cellular proliferation, induction of apoptosis, modulation of immunity and steroidogenesis.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye Rim Cho ◽  
Nisha Kumari ◽  
Nishant Thakur ◽  
Hien Thi Vu ◽  
Hyeonjin Kim ◽  
...  

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.


Author(s):  
HARITH JAMEEL MAHDI ALSAMMARRAIE ◽  
NURZALINA ABDUL KARIM KHAN ◽  
ROZIAHANIM MAHMUD

Objective: Consumption of crude natural products like plants and herbs for mitigation or treatment of illnesses usually accompanied with inconsistent therapeutic effects because of poor solubility and low bioavailability of active phytochemical(s) in addition to product instability. To overcome all of above mentioned drawback ethanol extract of Moringa oleifera leaf was formulated as standardised solid dosage form. Methods: Different types of materials as an adsorbent, surfactant and other necessary excipients were tested to be use in formulation of Moringa granules utilising wet granulation method. The formulated Moringa granules was then evaluated for organoleptic properties and physical characteristics, in vitro dissolution test, compatibility, drug content, heavy metal tests and microbial limit tests. Additionally, the in vivo anti-inflammatory against Carrageenan-induced paw oedema and anti-arthritic activity against CFA-induced arthritis were also assessed. Results: 95% ethanol extract of M. oleifera leaves was successfully formulated as standardised granules for oral administration utilising simple and low-cost techniques. Dissolution rate for the marker compounds was increased by an average of 1.076 fold. Animal groups given the prepared Moringa granules showed an improvement in the anti-inflammatory activity and the anti-arthritic activity compared to animal groups given crude extract at the same dose level. Additionally, all the treatment groups showed a significant difference at P<0.05 and P<0.01 compared to control group. Conclusion: To the best of our knowledge, this work was the first to use gum Arabic in the formulation of a standardised botanical pharmaceutical dosage form of M. oleifera crude extract. Additionally, formulation of Moringa granules apparently improves the drug release profile and bioactivity compare to Crude Moringa extract.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2203 ◽  
Author(s):  
Jin ◽  
Kim ◽  
Kim ◽  
Chung ◽  
Ha ◽  
...  

Abstract: Background: 6′-Sialyllactose (6SL) displays a wide range of the bioactive benefits, such as anti-proliferative and anti-angiogenic activities. However, the therapeutic effects of 6SL on benign prostatic hyperplasia (BPH) remain unknown. Methods: Six-week-old male Wistar rats (n = 40) were used for in vivo experiments. All rats were castrated and experimental BPH was induced in castrated rats by intramuscular injection of testosterone, with the exception of those in the control group. Rats with BPH were administrated finasteride and 0.5 or 1.0 mg/kg 6SL. Furthermore, the inhibitory effects of 6SL on human epithelial BPH cell line (BPH-1) cells were determined in vitro. Results: Rats with BPH exhibited outstanding BPH manifestations, including prostate enlargement, histological alterations, and increased prostate-specific antigen (PSA) levels. Compared to those in the BPH group, rats in the 6SL group showed fewer pathological changes and normal androgen events, followed by restoration of retinoblastoma protein (pRb) and cell cycle-related proteins. In BPH-1 cells, treatment with 6SL significantly suppressed the effects on the androgen receptor (AR), PSA, and E2F transcription factor 1 (E2F1)-dependent cell cycle protein expression. Conclusions: 6SL demonstrated anti-proliferative effects in a testosterone-induced BPH rat model and on BPH-1 cells by regulating the pRB/E2F1–AR pathway. According to our results, we suggest that 6SL may be considered a potential agent for the treatment of BPH.


Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1670 ◽  
Author(s):  
Wölfle-Roos JV ◽  
Katmer Amet B ◽  
Fiedler J ◽  
Michels H ◽  
Kappelt G ◽  
...  

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejie Gao ◽  
Bo Li ◽  
Anqi Ye ◽  
Houcai Wang ◽  
Yongsheng Xie ◽  
...  

Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.


2014 ◽  
Vol 39 (1) ◽  
pp. 30-34 ◽  
Author(s):  
SG Tulsani ◽  
N Chikkanarasaiah ◽  
S Bethur

Objectives: Biopure MTAD™, a new root canal irrigant has shown promising results against the most common resistant microorganism, E. faecalis, in permanent teeth. However, there is lack of studies comparing its antimicrobial effectiveness with NaOCl in primary teeth. The purpose of this study was to compare the in vivo antimicrobial efficacy of NaOCl 2.5% and Biopure MTAD™ against E. faecalis in primary teeth. Study design: Forty non vital single rooted primary maxillary anterior teeth of children aged 4-8 years, were irrigated either with NaOCl 2.5% (n=15), Biopure MTAD™ (n=15) and 0.9% Saline (n=10, control group). Paper point samples were collected at baseline (S1) and after chemomechanical preparation (S2) during the pulpectomy procedure. The presence of E. faecalis in S1 & S2 was evaluated using Real time Polymerase Chain Reaction. Results: Statistical significant difference was found in the antimicrobial efficacy of NaOCl 2.5 % and BioPure MTAD™ when compared to saline (p&gt;0.05). However, no statistical significant difference was found between the efficacies of both the irrigants. Conclusions: NaOCl 2.5% and BioPure MTAD™, both irrigants are equally efficient against E. faecalis in necrotic primary anterior teeth. MTAD is a promising irrigant, however clinical studies are required to establish it as ideal root canal irrigant in clinical practice.


2008 ◽  
Vol 74 (7) ◽  
pp. 1997-2003 ◽  
Author(s):  
Mathieu Millette ◽  
Gilbert Cornut ◽  
Claude Dupont ◽  
François Shareck ◽  
Denis Archambault ◽  
...  

ABSTRACT This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under simulated gastrointestinal conditions. A well diffusion assay using supernatants from LAB demonstrated strong activity against a clinical isolate of VRE. A first in vivo study was done using C57BL/6 mice that received daily intragastric doses of L. lactis MM19, P. acidilactici MM33, P. acidilactici MM33A (a pediocin mutant that had lost its ability to produce pediocin), or phosphate-buffered saline (PBS) for 18 days. This study showed that L. lactis and P. acidilactici MM33A increased the concentrations of total LAB and anaerobes while P. acidilactici MM33 decreased the Enterobacteriaceae populations. A second in vivo study was done using VRE-colonized mice that received the same inocula as those in the previous study for 16 days. In L. lactis-fed mice, fecal VRE levels 1.73 and 2.50 log10 CFU/g lower than those in the PBS group were observed at 1 and 3 days postinfection. In the P. acidilactici MM33-fed mice, no reduction was observed at 1 day postinfection but a reduction of 1.85 log10 CFU/g was measured at 3 days postinfection. Levels of VRE in both groups of mice treated with bacteriocin-producing LAB were undetectable at 6 days postinfection. No significant difference in mice fed the pediocin-negative strain compared to the control group was observed. This is the first demonstration that human L. lactis and P. acidilactici nisin- and pediocin-producing strains can reduce VRE intestinal colonization.


2015 ◽  
Vol 1 (1) ◽  
pp. 25
Author(s):  
Laila Fitrotuz Zahroh ◽  
Rahmawati Sri Praptiningsih ◽  
Moh. Baehaqi

Background: Oral mucosa ulceration which often occurs usually in the form of white-yellowish spot with concave surface, reddish edge and pain. Based on previous research, Aloe vera process anti-inflammation substance that could help quickening ulceration healing process. This research aims to know the effect of Aloe vera flesh extract on Male wistar rats oral mucosa ulceration in-vivo. Method: this research was quasi experimental research with the post-test only control group design using Male wistar rats as the testing animal. In the research, there were three treatment groups: The first groups which was given aquadest treatment, second groups with Aloe vera flesh extract, and third groups which was given chlorhexidine gluconate 0,2% treatment. The data collecting was based on histopathology observation concerning the increase of fibroblast quantity. Result: The research result based on comparison test among the three groups with One Way Anova showed that on Day 3th, the average quantity of fibroblast didn't have significant difference between the treatment group and control group positive that was p>0,05, meanwhile on Day 7th every group showed significant difference p<0,05. Conclusion: It concluded that Aloe vera flesh extract has influence on the healing of Male wistar rats oral mucosa ulceration as shown by fibroblast increasing quantity.


2021 ◽  
Author(s):  
Soheila Moeini ◽  
Ehsan Karimi ◽  
Ehsan Oskoueian

Abstract Background: This research was performed to synthesize nanophytosomes-loaded high phenolic fraction (HPF) from Juniperus polycarpos fruit extract and investigate its antiproliferation effects against breast cancer in mice model. Results: The nanophytosomes-loaded HPF from Juniperus polycarpos fruit extract was synthesized. The mice trial was conducted to determine the possible toxic effects of the synthesized nanophytosomes. The anticancer, pro-apoptotic, and antioxidative activities of the nanophytosomes were determined. The nanophytosomes-loaded HPF had a spherical structure with a size of 176 nm and a polydispersity index coefficient of 0.24. The in-vivo study manifested that nanophytosomes-loaded HPF significantly improved weight gain and food intake compared to the negative control group (p<0.05). The nanophytosomes-loaded HPF significantly enhanced the expression of bax (3.4-fold) and caspase-3 (2.7-fold) genes but reduced bcl2 (3.6-fold) gene expression in tumor cells. The average tumor size was significantly decreased in mice treated with nanophytosomes-loaded HPF (p<0.05). The expression of GPX (2.3-fold) and SOD (2.7-fold) antioxidants in the liver of mice supplemented with nanophytosomes-loaded HPF was significantly developed compared to the negative control (p<0.05). The nanophytosomes-loaded HPF did not show toxicity on normal cells. Conclusion: Our results indicated that nanophytosomes-loaded HPF might be a potential anticancer agent for the breast cancer treatment.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianyong Gao ◽  
Yi Zhao ◽  
Tinglan Sun ◽  
Weike Liu ◽  
Zhenguo Wang

Objective: To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy. Methods: A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group (105 cases) and the control group (100 cases). The experimental group was relaxed with acupotomy in three positions: Heaven (tian), Human (ren) and Earth (di). Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group. One treatment was conducted in one week, and the duration of one course of treatment was three weeks. The VAS, JOA score and NDI index were observed after treatment.  Results: Before and after treatment, the total treatment efficiency of the treatment group was 95.23%, and that of the control group was 80.00%, there was significant difference between the two groups, P<0.05; Before operation, there was no significant difference in JOA score, NDI index score, and VAS score between the treatment group and the control group (P>0.05); there was no significant difference after 1 week (P>0.05), but there were significant differences between the two groups 2 weeks and 3 weeks after operation (P<0.05). Conclusion: Acupotomy trinity lysis is a safe, effective and economical treatment for cervical spondylotic myelopathy.


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