scholarly journals In Vitro and In Vivo Tumor Growth Inhibition by Glutathione Disulfide Liposomes

2017 ◽  
Vol 10 ◽  
pp. 117906441769607 ◽  
Author(s):  
Satya S Sadhu ◽  
Shenggang Wang ◽  
Rakesh Dachineni ◽  
Ranjith Kumar Averineni ◽  
Yang Yang ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Cell Function ◽  
Survival Rates ◽  
Significant Inhibition ◽  
Control Group ◽  
Tumor Growth Inhibition ◽  
Tumor Proliferation ◽  
Glutathione Disulfide

Glutathione disulfide (GSSG) is an endogenous peptide and the oxidized form of glutathione. The impacts of GSSG on cell function/dysfunction remain largely unexplored due to a lack of method to specifically increase intracellular GSSG. We recently developed GSSG liposomes that can specifically increase intracellular GSSG. The increase affected 3 of the 4 essential steps (cell detachment, migration, invasion, and adhesion) of cancer metastasis in vitro and, accordingly, produced a significant inhibition of cancer metastasis in vivo. In this investigation, the effect of GSSG liposomes on cancer growth was investigated with B16-F10 and NCI-H226 cells in vitro and with B16-F10 cells in C57BL/6 mice in vivo. Experiments were conducted to elucidate the effect on cell death through promotion of apoptosis and the effect on the cell cycle. The in vivo results with C57BL/6 mice implanted subcutaneously with B16-F10 cells showed that GSSG liposomes retarded tumor proliferation more effectively than that of dacarbazine, a chemotherapeutic drug for the treatment of melanoma. The GSSG liposomes by intravenous injection (GLS IV) and GSSG liposomes by intratumoral injection (GLS IT) showed a tumor proliferation retardation of 85% ± 5.7% and 90% ± 3.9%, respectively, compared with the phosphate-buffered saline (PBS) control group. The median survival rates for mice treated with PBS, blank liposomes, aqueous GSSG, dacarbazine, GLS IV, and GLS IT were 7, 7, 7.5, 7.75, 11.5, and 16.5 days, respectively. The effective antimetastatic and antigrowth activities warrant further investigation of the GSSG liposomes as a potentially effective therapeutic treatment for cancer.

scholarly journals Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Survival Rates ◽  
Control Group ◽  
P Value ◽  
Transcriptome Profile ◽  
Embryo Viability ◽  
The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

scholarly journals In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens

2021 ◽  
Author(s):  
Nicholas P. Clayton ◽  
Akash Jain ◽  
Stephanie A. Halasohoris ◽  
Lisa M. Pysz ◽  
Sanae Lembirik ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Vehicle Control ◽  
Control Group ◽  
Post Challenge ◽  
Vehicle Control Group ◽  
Tebipenem Pivoxil

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 – 0.008 μg/ml for B. anthracis, ≤0.0005 – 0.03 μg/ml for Y. pestis, 0.25 – 1 μg/ml for B. mallei, and 1 – 4 μg/ml for B. pseudomallei. In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

scholarly journals In Vitro and In Vivo Activities of Newer Fluoroquinolones against Vibrio vulnificus

2002 ◽  
Vol 46 (11) ◽  
pp. 3580-3584 ◽  
Author(s):  
Hung-Jen Tang ◽  
Ming-Chung Chang ◽  
Wen-Chien Ko ◽  
Kun-Yen Huang ◽  
Chih-Lung Lee ◽  
...  
Keyword(s):  
Vibrio Vulnificus ◽  
Survival Rates ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Clinical Strain ◽  
Control Group ◽  
Dilution Method ◽  
Agar Dilution Method

ABSTRACT The MICs of six fluoroquinolones as well as minocycline and cefotaxime for 46 clinical isolates of Vibrio vulnificus were determined by the agar dilution method. All the drugs tested had good activities against all isolates, with the MICs at which 90% of the isolates tested were inhibited (MIC90s) by five of the fluoroquinolones ranging between 0.03 and 0.06 μg/ml. The MIC90 of lomefloxacin, on the other hand, was 0.12 μg/ml. Time-kill studies were conducted with these agents and a clinical strain of V. vulnificus, VV5823. When approximately 5 × 105 CFU of V. vulnificus/ml was incubated with any one of the above-mentioned six fluoroquinolones at concentrations of two times the MIC, there was an inhibitory effect on V. vulnificus that persisted for more than 48 h with no noted regrowth. The efficacies of the fluoroquinolones were further evaluated in vivo in the mouse model of experimental V. vulnificus infection and compared to the efficacy of a combination therapy using cefotaxime plus minocycline. With an inoculum of 1.5 × 107 CFU, 28 (87.5%) of 32 mice in the cefotaxime-minocycline-treated group survived and 29 (91%) of the 32 mice in the moxifloxacin-treated group survived while none of the 32 mice in the control group did. With an inoculum of 3.5 × 107 CFU, the difference in survival rates among groups of 15 mice treated with levofloxacin (13 of 15), moxifloxacin (10 of 15), gatifloxacin (10 of 15), sparfloxacin (11 of 15), ciprofloxacin (12 of 15), or lomefloxacin (10 of 15) was not statistically significant while none of the 15 mice treated with saline survived. We concluded that the newer fluoroquinolones as single agents are as effective as the cefotaxime-minocycline combination in inhibiting V. vulnificus both in vitro and in vivo.

scholarly journals Inhibitory effect of naphthoquine phosphate against Babesia gibsoni in vitro and Babesia rodhaini in vivo

2021 ◽  
Author(s):  
Shengwei Ji ◽  
Mingming Liu ◽  
Eloiza May Galon ◽  
Mohamed Abdo Rizk ◽  
Bumduuren Tuvshintulga ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Strategies ◽  
Drug Repurposing ◽  
Significant Inhibition ◽  
Parasite Growth ◽  
New Drugs ◽  
Control Group ◽  
Babesia Gibsoni

Abstract Background: Drug resistance and severe side effects are major challenges in the treatment of babesiosis as they lead to less choices for treatment. Development of new drugs to enrich the treatment strategies and delay the emergence of drug resistance in parasites is still needed. Naphthoquine (NQ) combined with artemisinin treats Plasmodium infection by rapid parasite clearance. The current study repurposed NQ as a babesiosis drug treatment by evaluating the effects of naphthoquine phosphate (NQP) as a single dose treatment for babesiosis. Methods: In vitro anti-Babesia activity of NQP was tested on Babesia gibsoni cultures. The inhibition of parasite growth was verified using a SYBR green I-based fluorescence assay. In vivo efficacy of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored. Results: The half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 μM. Oral administration of NQP for 5 successive days at a dose of 40 mg/kg of body weight resulted in significant inhibition on parasite growth compared with the control group. All mice in NQP-treated group survived, whereas the mice in control group died between days 6 and 9 post infection. Conclusion: This is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. The results showed that NQP is a promising drug for babesiosis treatment and drug repurposing may provide new treatment strategies for babesiosis.

scholarly journals Efficacy of Ceftriaxone, Cefepime, Doxycycline, Ciprofloxacin, and Combination Therapy for Vibrio vulnificus Foodborne Septicemia

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Sonya A. Trinh ◽  
Hannah E. Gavin ◽  
Karla J. F. Satchell
Keyword(s):  
Combination Therapy ◽  
Vibrio Vulnificus ◽  
Survival Rates ◽  
Control Group ◽  
Content Type ◽  
Infection Models ◽  
Gram Negative Organisms ◽  
Foodborne Infection

ABSTRACT Foodborne Vibrio vulnificus infections are associated with higher rates of sepsis and mortality than wound infections; however, antibiotic efficacy studies have not been performed in foodborne infection models. The efficacies of ceftriaxone, cefepime, doxycycline, ciprofloxacin, and combination therapy were assessed in V. vulnificus intestinal infection in mice in order to model foodborne infections. In accordance with prior studies of cefotaxime, cefepime was synergistic with doxycycline and ciprofloxacin in vitro; combination therapy significantly decreased bacterial growth, by ≥2 log10 units, from that with antibiotic monotherapy (P < 0.01). In vivo, survival rates in the ceftriaxone (50%), doxycycline (79%), and ciprofloxacin (80%) groups were significantly higher than those in the control group (0%) (P < 0.0001). Survival was significantly higher with ceftriaxone-doxycycline (91%) or ceftriaxone-ciprofloxacin (100%) therapy than with ceftriaxone (50%) (P ≤ 0.05). Survival with cefepime-doxycycline (96%) or cefepime-ciprofloxacin (90%) therapy was significantly higher than that with cefepime alone (20%) (P < 0.001). There was no difference in survival between the combination therapy groups. Thus, we conclude that combination therapy was the most effective treatment for foodborne V. vulnificus septicemia. In a septic patient with a recent ingestion of raw seafood, cefepime in combination with doxycycline or ciprofloxacin should be initiated for coverage of resistant Gram-negative organisms and V. vulnificus pending a microbiological diagnosis. Once a diagnosis of foodborne V. vulnificus septicemia is established, treatment can safely transition to ceftriaxone in combination with doxycycline or ciprofloxacin.

scholarly journals Protective Effects of Novel Lactobacillaceae Strains Isolated from Chicken Caeca against Necrotic Enteritis Infection: In Vitro and In Vivo Evidences

2022 ◽  
Vol 10 (1) ◽  
pp. 152
Author(s):  
Nuria Vieco-Saiz ◽  
Yanath Belguesmia ◽  
Ruth Raspoet ◽  
Eric Auclair ◽  
Connor Padgett ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Production ◽  
Survival Rates ◽  
Control Group ◽  
Necrotic Enteritis ◽  
Protective Effects ◽  
Infected Chicken ◽  
Significant Survival

The present study aimed to show the benefits of novel lactic acid bacteria (LAB) strains isolated from the caeca of healthy chickens. These novel strains, identified as Limosilactobacillus reuteri and Ligilactobacillus salivarius, displayed high levels of lactic acid production, capability of biofilm formation, high aggregation and adhesion scores, and significant survival rates under conditions mimicking the chicken gastrointestinal tract (GIT). In addition, these novel Lactobacillaceae isolates were neither hemolytic nor cytotoxic. In vivo trials were able to establish their ability to reduce necrotic enteritis. Notably, a significant weight gain was registered, on day 10 of treatment, in the group of chickens fed with a mixture of L. reuteri ICVB416 and L. salivarius ICVB430 strains, as compared with the control group. This group has also shown a reduced number of lesions in the gut compared with other infected chicken groups. This study provides in vitro and in vivo evidence supporting the benefits of these novel Lactobacillaceae isolates for their use in poultry livestock as protective cultures to control the bacterial necrotic enteritis (NE) Clostridium perfringens.

scholarly journals Vitrification Effects on the Transcriptome of in vivo-Derived Porcine Morulae

2021 ◽  
Vol 8 ◽  
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Alejandro González-Plaza ◽  
Inmaculada Parrilla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Survival Rates ◽  
Gene Expression Pattern ◽  
Control Group ◽  
High Survival ◽  
Embryo Survival ◽  
Developmental Potential

Despite the reported promising farrowing rates after non-surgical and surgical transfers of vitrified porcine morulae and blastocysts produced in vivo (range: 70–75%), the pregnancy loss is 5–15 fold higher with vitrified than with fresh embryos. The present study aimed to investigate whether vitrification affects the transcriptome of porcine morulae, using microarrays and RT-qPCR validation. Morulae were obtained surgically from weaned sows (n = 13) on day 6 (day 0 = estrus onset). A total of 60 morulae were vitrified (treatment group). After 1 week of storage, the vitrified morulae were warmed. Vitrified-warmed and non-vitrified fresh morulae (control; n = 40) were cultured for 24 h to assess embryo survival by stereomicroscopy after. A total of 30 vitrified/warmed embryos that were deemed viable and 30 fresh control embryos (three pools of 10 for each experimental group) were selected for microarray analysis. Gene expression was assessed with a GeneChip® Porcine Genome Array (Affymetrix). An ANOVA analysis p-unadjusted &lt;0.05 and a fold change cut-off of ±1.5 were set to identify differentially expressed genes (DEGs). Data analysis and biological interpretation were performed using the Partek Genomic Suite 7.0 software. The survival rate of morulae after vitrification and warming (92.0 ± 8.3%) was similar to that of the control (100%). A total of 233 DEGs were identified in vitrified morulae (38 upregulated and 195 downregulated), compared to the control group. Nine pathways were significantly modified. Go-enrichment analysis revealed that DEGs were mainly related to the Biological Process functional group. Up-regulated DEGs were involved in glycosaminoglycan degradation, metabolic pathways and tryptophan metabolism KEGG pathways. The pathways related to the down-regulated DEGs were glycolysis/gluconeogenesis, protein export and fatty acid elongation. The disruption of metabolic pathways in morulae could be related to impaired embryo quality and developmental potential, despite the relatively high survival rates after warming observed in vitro. In conclusion, vitrification altered the gene expression pattern of porcine morulae produced in vivo, generating alterations in the transcriptome that may interfere with subsequent embryo development and pregnancy after embryo transfer.

scholarly journals How does chemotherapy treatment damage the prepubertal testis?

Reproduction ◽  
2018 ◽  
Vol 156 (6) ◽  
pp. R209-R233 ◽  
Author(s):  
Caroline M Allen ◽  
Federica Lopes ◽  
Rod T Mitchell ◽  
Norah Spears
Keyword(s):  
Cancer Survival ◽  
Cell Function ◽  
Current Knowledge ◽  
Survival Rates ◽  
Chemotherapy Treatment ◽  
Therapy Targets ◽  
Chemotherapy Agents ◽  
The Impact

Chemotherapy treatment is a mainstay of anticancer regimens, significantly contributing to the recent increase in childhood cancer survival rates. Conventional cancer therapy targets not only malignant but also healthy cells resulting in side effects including infertility. For prepubertal boys, there are currently no fertility preservation strategies in use, although several potential methods are under investigation. Most of the current knowledge in relation to prepubertal gonadotoxicity has been deduced from adult studies; however, the prepubertal testis is relatively quiescent in comparison to the adult. This review provides an overview of research to date in humans and animals describing chemotherapy-induced prepubertal gonadotoxicity, focusing on direct gonadal damage. Testicular damage is dependent upon the agent, dosage, administration schedule and age/pubertal status at time of treatment. The chemotherapy agents investigated so far target the germ cell population activating apoptotic pathways and may also impair Sertoli cell function. Due to use of combined chemotherapy agents for patients, the impact of individual drugs is hard to define, however, use of in vivo and in vitro animal models can overcome this problem. Furthering our understanding of how chemotherapy agents target the prepubertal testis will provide clarity to patients on the gonadotoxicity of different drugs and aid in the development of cytoprotective agents.

scholarly journals Potential Mechanisms Responsible for the Antinephrolithic Effects of an Aqueous Extract of Fructus Aurantii

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoran Li ◽  
Qiang Liang ◽  
Yunji Sun ◽  
Long Diao ◽  
Ze Qin ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Significant Inhibition ◽  
Control Group ◽  
High Dose ◽  
Crystal Formation ◽  
Crystal Dissolution ◽  
Therapeutic Groups ◽  
Immunohistochemical Analyses

The potential effects of Fa extract on the prevention and treatment of CaOx nephrolithiasis were analyzed in an ethylene glycol- (EG-) induced CaOx crystallization model in rats and anin vitroassay. Multiple biochemical variables were measured in the urine and kidney. Kidney sections were subjected to histopathological and immunohistochemical analyses. Urolithiasis-related osteopontin (OPN) was evaluated by Western blotting. Thein vitroassay revealed the significant inhibition of crystal formation (3.50±1.43) and dilution of formed crystals (12.20±3.35) in the group treated with 1 mg/mL Fa extract compared with the control group (52.30±4.71and53.00±4.54, resp.) (p<0.05). Thein vivoexperiments showed that prophylactic treatment with Fa aqueous extract significantly prevented EG-induced renal crystallization and pathological alterations compared with nephrolithic rats (p<0.05). Significantly lower levels of oxidative stress, oxalate, and OPN expression as well as increased citrate and urine output levels were observed in both the low- and high-dose prophylactic groups (p<0.05). However, in the low- and high-dose therapeutic groups, none of these indexes were significantly improved (p>0.05) except for urinary oxalate in the high-dose therapeutic groups (p<0.05). Fa extract prevented CaOx crystallization and promoted crystal dissolutionin vitro. Additionally, it was efficacious in preventing the formation of CaOx nephrolithiasis in rats.

Chronic DOC treatment enhances Na(+)-H+ exchanger activity of beta-intercalated cells in rabbit CCD

1992 ◽  
Vol 262 (5) ◽  
pp. F712-F717 ◽  
Author(s):  
Y. Yamaji ◽  
M. Hayashi ◽  
M. Iyori ◽  
W. Kitajima ◽  
T. Saruta
Keyword(s):  
Cell Function ◽  
Functional Change ◽  
Control Group ◽  
Intercalated Cells ◽  
Acetoxymethyl Ester ◽  
Acid Base Status ◽  
The Difference ◽  
And Control

Chronic deoxycorticosterone (DOC) treatment is known to increase HCO3- secretion in rabbit cortical collecting ducts (CCD). In this study, we examined whether changes in number or function of intercalated cells (ICC) are induced by DOC treatment. The number of total ICC [acetoxymethyl ester of 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF/AM)-positive cells after its luminal loading], and beta-ICC (peanut agglutinin-positive cells) was not different between DOC and control groups in either initial CCD or terminal CCD. To evaluate the single-cell function of ICC, the rate of intracellular pH (pHi) recovery (dpHi/dt, pHU/s x 10(3)) after NH4+/NH3 prepulse was studied in the in vitro microperfused CCD in the presence of HCO3-/CO2 with BCECF/AM. The mean rate of dpHi/dt of beta-ICC in the DOC group was faster than that in the control group (6.19 +/- 0.36 vs. 4.30 +/- 0.41, P less than 0.005, respectively), whereas baseline pHi and buffer capacity were similar in the two groups. The inhibition of basolateral Na(+)-H+ exchanger with 1 mM amiloride eliminated the difference of dpHi/dt between the two groups, indicating the increased activity of basolateral Na(+)-H+ exchanger of beta-ICC in the DOC group. The correction of DOC-induced metabolic alkalosis by oral acid loading abolished the increase in Na+/H+ exchanger activity by chronic DOC treatment. These results suggest that DOC treatment induces a functional change in a single beta-ICC and that this functional change was induced by in vivo acid-base status.

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