scholarly journals Assessing the Impact of Tissue Target Concentration Data on Uncertainty in In Vivo Target Coverage Predictions

2016 ◽  
Vol 5 (10) ◽  
pp. 565-574 ◽  
Author(s):  
A Tiwari ◽  
H Luo ◽  
X Chen ◽  
P Singh ◽  
I Bhattacharya ◽  
...  
Keyword(s):  
Target Coverage ◽  
Concentration Data ◽  
Target Concentration ◽  
The Impact ◽  
Tissue Target

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

2020 ◽  
Vol 23 ◽  
Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
Nuclear Dna ◽  
Liquid Paraffin ◽  
Tail Length ◽  
Hepatic Tissue ◽  
Tissue Destruction ◽  
Group 2 ◽  
The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

scholarly journals Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1497
Author(s):  
Pansong Zhang ◽  
Qiao Guo ◽  
Zhihua Wei ◽  
Qin Yang ◽  
Zisheng Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mammalian Cells ◽  
Secretion System ◽  
Chinese Herbs ◽  
Infection Model ◽  
Lung Pathology ◽  
Promising Alternative ◽  
The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

scholarly journals Transcriptional Profiling of Porcine Blastocysts Produced In Vitro in a Chemically Defined Culture Medium

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1414
Author(s):  
Josep M. Cambra ◽  
Emilio A. Martinez ◽  
Heriberto Rodriguez-Martinez ◽  
Maria A. Gil ◽  
Cristina Cuello
Keyword(s):  
Culture Medium ◽  
Embryo Quality ◽  
Transcriptional Profiling ◽  
Defined Medium ◽  
Platelet Factor ◽  
Defined Media ◽  
Defined Culture ◽  
The Impact

The development of chemically defined media is a growing trend in in vitro embryo production (IVP). Recently, traditional undefined culture medium with bovine serum albumin (BSA) has been successfully replaced by a chemically defined medium using substances with embryotrophic properties such as platelet factor 4 (PF4). Although the use of this medium sustains IVP, the impact of defined media on the embryonic transcriptome has not been fully elucidated. This study analyzed the transcriptome of porcine IVP blastocysts, cultured in defined (PF4 group) and undefined media (BSA group) by microarrays. In vivo-derived blastocysts (IVV group) were used as a standard of maximum embryo quality. The results showed no differentially expressed genes (DEG) between the PF4 and BSA groups. However, a total of 2780 and 2577 DEGs were detected when comparing the PF4 or the BSA group with the IVV group, respectively. Most of these genes were common in both in vitro groups (2132) and present in some enriched pathways, such as cell cycle, lysosome and/or metabolic pathways. These results show that IVP conditions strongly affect embryo transcriptome and that the defined culture medium with PF4 is a guaranteed replacement for traditional culture with BSA.

scholarly journals Inhibited MicroRNA-301 Restrains Angiogenesis and Cell Growth in Esophageal Squamous Cell Carcinoma by Elevating PTEN

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bin Wang ◽  
Peiyan Hua ◽  
Ruimin Wang ◽  
Jindong Li ◽  
Guangxin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Cycle Distribution ◽  
Pten Inhibition ◽  
The Impact

Abstract Objective Esophageal squamous cell carcinoma (ESCC) is featured by early metastasis and late diagnosis. MicroRNA-301 (miR-301) is known to participate in diverse cancers. Nevertheless, effects of miR-301 on ESCC remain unexplored. Thus, we aim to explore the role of miR-301 in ESCC progression. Methods Expression of miR-301 and phosphatase and tensin homologue (PTEN) in ESCC tissues and cell lines was assessed. Next, the screened cells were treated with altered miR-301 or PTEN oligonucleotide and plasmid, and then, the colony formation ability, cell viability, migration, invasion, cell cycle distribution and apoptosis of ESCC cells were assessed. Moreover, tumor growth and microvessel density (MVD) were also assessed, and the targeting relationship between miR-301 and PTEN was affirmed. Results MiR-301 was upregulated, and PTEN was downregulated in ESCC tissues and cells. KYSE30 cells and Eca109 cells were selected for functional assays. In KYSE30 cells, inhibited miR-301 or overexpressed PTEN suppressed cell malignant behaviors, and silenced PTEN eliminated the impact of miR-301 inhibition on ESCC progression. In Eca109 cells, miR-301 overexpression or PTEN inhibition promoted cell malignant behaviors, and PTEN overexpression reversed the effects of miR-301 elevation on ESCC progression. The in vivo assay revealed that miR-301 inhibition or PTEN overexpression repressed ESCC tumor growth and MVD, and miR-301 elevation or PTEN reduction had contrary effects. Moreover, PTEN was targeted by miR-301. Conclusion Taken together, results in our study revealed that miR-301 affected cell growth, metastasis and angiogenesis via regulating PTEN expression in ESCC.

scholarly journals Trends in Managing Cardiac and Orthopaedic Device-Associated Infections by Using Therapeutic Biomaterials

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1556
Author(s):  
Stefania Scialla ◽  
Giorgia Martuscelli ◽  
Francesco Nappi ◽  
Sanjeet Singh Avtaar Singh ◽  
Adelaide Iervolino ◽  
...  
Keyword(s):  
Clinical Medicine ◽  
Preventive Treatment ◽  
Active Surface ◽  
In Vivo Studies ◽  
Antibiotic Resistant ◽  
Implanted Medical Devices ◽  
Hospital Acquired ◽  
Systemic Antibiotics ◽  
The Impact

Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

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