scholarly journals De-escalation antibiotic therapy alleviates organ injury through modulation of NETs formation during sepsis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zehua Duan ◽  
Tian Xie ◽  
Chengnan Chu ◽  
Fang Chen ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Late Stage ◽  
Early Stage ◽  
Organ Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Escalation Therapy ◽  
Significant Difference

AbstractEmpiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detailed mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular traps (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy in cecum ligation and puncture (CLP) models. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. In CLP models, de-escalation therapy resulted in an increased serum MPO-DNA level during the early stage and decreased MPO-DNA level during late stage, which exerted the reverse effects in escalation therapy. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAse I during the early stage of sepsis (p < 0.01). Histopathological analysis showed decreased injury in lung, liver, and intestine in de-escalation therapy compared with escalation therapy (p < 0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p < 0.01), however, no significant difference was found between de-escalation and escalation group (p = 0.051). The in vitro study showed that the imipenem could promote, while the ceftriaxone could inhibit the formation of NETs in PMA-activated PMNs through a ROS-dependent manner. We firstly demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage, and inhibiting NETs formation in the late stage of sepsis.

scholarly journals De-escalation Antibiotic Therapy Alleviates Organ Injury through Modulation of NET Formation during Sepsis

2020 ◽  
Author(s):  
Tian Xie ◽  
Chengnan Chu ◽  
Shilong Sun ◽  
Xinyu Wang ◽  
Zehua Duan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Late Stage ◽  
Early Stage ◽  
Neutrophil Extracellular Trap ◽  
Organ Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Escalation Therapy ◽  
Significant Difference

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detail mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular trap (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy based on their effects on NETs formation in CLP model. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. The in vitro study showed that imipenem and ceftriaxone had opposite effects on NETs formation in activated neutrophils. De-escalation therapy resulted in an evaluated MPO-DNA during early stage and decreased MPO-DNA during late stage, which exerted the reverse effects in escalation therapy sepsis animal model. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAseI during early stage of sepsis (p<0.01). Histopathological analysis showed decreased injury in lung, liver and intestine in de-escalation therapy compared with escalation therapy (p<0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p<0.01), however, no significant difference was found between de-escalation and escalation group (p=0.051). We demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage and inhibiting NETs formation in the late stage of sepsis.

scholarly journals Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yunzhao Yang ◽  
Shaoqun Tang ◽  
Chunchun Zhai ◽  
Xin Zeng ◽  
Qingjian Liu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Inflammatory Response ◽  
Vascular Dysfunction ◽  
Control Group ◽  
Dependent Manner ◽  
Ang Ii ◽  
Stat3 Pathway

Background. Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. Methods. Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. Results. Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. Conclusions. IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.

scholarly journals High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing Zhao ◽  
Min Liu ◽  
Ping Liu ◽  
Yibing Peng ◽  
Jun Huang ◽  
...  
Keyword(s):  
Vitamin C ◽  
Inflammatory Response ◽  
Early Stage ◽  
Treatment Options ◽  
Control Group ◽  
High Dose ◽  
Protein Levels ◽  
Number Of Patients ◽  
Significant Difference ◽  
Intravenous Vitamin

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation.Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender.Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6–7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04).” The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7.Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

The Study of Effect and Mechanism by Vitamin K2 on Human MDS Cell Line MUTZ-1.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4357-4357
Author(s):  
Bao-An Chen ◽  
Xin Xu ◽  
Ze-Ye Shao ◽  
Jia-Hua Ding ◽  
Guo-Hua Xia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Caspase 3 ◽  
Cellular Proliferation ◽  
Vitamin K2 ◽  
Time Dependent ◽  
Control Group ◽  
Dependent Manner ◽  
Significant Difference

Abstract The myelodysplastic syndromes (MDS) are characterized by hemopoietic insufficiency associated with cytopenias leading to serious morbidity and the additional risk of leukemic transformation. Vitamin K2(VK2) is reported to induce apoptosis or differentiation of leukemic cell lines in vitro. For investigating the effects and mechanism of VK2 on human MDS cell line MUTZ-1 in vitro,we observed the changes of morphologic features of MUTZ-1 cells by exposing to VK2.The transmission electron microscope was used to observe the apoptosis of MUTZ-1 cells. Cellular proliferation was determined by the MTT assay. The flow cytometry was used to analysis apoptosis rate and the change of cell cycle. The expression of apoposis-related genes bcl-2, survivin and bax were detected by reverse transcriptase polymerase chain reaction(RT-PCR).The activity of caspase-3 was detected by chemiluminescence assay. After exposing to 10μmol L−1 and higher concentration of VK2, it could inhibit MUTZ-1 cells proliferation in a dose-and time-dependent manner(p&lt;0.05). At concentration of 5μmol/l VK2 treatment, it might accelerate cellular proliferation, but there’s no significant difference compared with control group. Apoptosis peak on FCM and positive Annexin-V FITC/PI on cell membrane showed that VK2 induced apoptosis of MUTZ-1 cells in a dose-and-time-dependent manner, G0/G1 cell cycle arrest, significantly dow-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax.The activities of caspase-3 were significantly increased. Low concentration of VK2 could facilitate cell proliferation. The higher concentration of VK2 could induce apoptosis of MUTZ-1 cells. These results indicate that VK2 induces MUTZ-1 cells apoptosis by activating caspase-3 pathway, the apoptosis related genes bcl-2, survivin down-regulated might play an important role in this process.

Comparative Study to Evaluate the Surface Detail Reproduction of Dental Stone after Immersion in Various Different Disinfectant Solutions, Under Stereomicroscope 10 X Magnification –An In-Vitro Study

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Rathika Rai ◽  
M. A. Easwaran ◽  
K. T. Dhivya
Keyword(s):  
Sodium Hypochlorite ◽  
In Vitro Study ◽  
Control Group ◽  
Immersion Method ◽  
Significant Difference ◽  
Surface Irregularities ◽  
Disinfectant Solution ◽  
Surface Detail ◽  
Group B

Aim: To evaluate the surface detail reproduction of dental stone this is immersed in different disinfectant solution and studied under stereomicroscope. Methodology: Total number of 30 specimens of dental stone (Type III) were made with measurements of 1.5cm diameter and 1cm height .This samples are divided in to 3 groups group A,B,C. were A is immersed in Distilled water which was taken as control group ;B is immersed in 2% Glutaraldehyde and C is immersed in 5%sodium hypochlorite. Each specimen were immersed in the disinfectant solution for 15 minutes and dried under room temperature for 24 hrs. After 24 hrs each specimens are studied under stereomicroscope for surface details. Result: The results showed no significant difference in the surface irregularities and porosities for a group 1 and group 2 except group 3 which showed significant increase in the porosities, surface irregularities and erosions after disinfection with 5% NaHOCl by immersion method. Conclusion: The surface detail reproduction capacity of die stone was adversely affected when 5% Sodium hypochlorite was used as disinfectant solution when compare d to control group and 2% Glutaraldehyde

The Toxicity Effect of Echium Amoenum on the Liver and Kidney of Mice.

2020 ◽  
Vol 17 ◽  
Author(s):  
Mozhgan Ghorbani ◽  
Atefeh Araghi ◽  
Nabi Shariatifar ◽  
Seyed Hooman Mirbaha ◽  
Behrokh Marzban Abbasabadi ◽  
...  
Keyword(s):  
Pyrrolizidine Alkaloids ◽  
Biochemical Analysis ◽  
Liver Enzymes ◽  
Copper Ion ◽  
Control Group ◽  
Dependent Manner ◽  
Toxicity Effect ◽  
Significant Difference ◽  
Liver And Kidney ◽  
Echium Amoenum

Aims: The aim of this study was to investigate the toxic effect of Echium amoenum plants on the liver and kidney of animal model. Background: Echium amoenum is one of the medicinal plants containing pyrrolizidine alkaloids with several properties which has widely consumed among different communities. Objective: The toxic effects of Echium amoenum on the liver and kidney were investigated in this study. Methods: Sixty mice were kept for 28 days under the appropriate laboratory conditions. Echium amoenum extract (25, 12.5, 50 mg / kg, ip.) was administered for 28 days. At the end of experiment, blood samples were drawn and liver and kidneys were removed for evaluating hepatotoxicity and nephrotoxicity of extract. Additionally, experiments were conducted to assay the enzymatic and oxidative activities. Results: There was no significant difference in the levels of copper ion in the liver and kidneys among all groups. There was a significant difference in the levels of lipid peroxidation in the liver of treated groups versus control group. The significant difference was not observed in the levels of glutathione of the liver of all groups. However, the levels of glutathione of the kidney significantly decreased in the treated groups versus control group. There was no significant difference in the liver enzymes including ALP, SGOT, and SGPT between all groups. This indicates that damage increase with enhancing the time and concentrations of extract. Biochemical analysis showed the creatinine and urea levels did not change in the treated groups versus control group. Conclusion: According to the present findings, it is suggested that Echium amoenum causes hepatotoxicity and nephrotoxicity effects in dose and time dependent manner.

Supplementation of c-type natriuretic peptide during in vitro growth period benefits the development of murine preantral follicles

Zygote ◽  
2020 ◽  
pp. 1-5
Author(s):  
Li Ang ◽  
Cao Haixia ◽  
Li Hongxia ◽  
Li Ruijiao ◽  
Guo Xingping ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Granulosa Cells ◽  
Culture System ◽  
Early Stage ◽  
Developmental Competence ◽  
Control Group ◽  
Follicle Development ◽  
Control Groups ◽  
Preantral Follicles

Summary The present study investigated the effects of c-type natriuretic peptide (CNP) on the development of murine preantral follicles during in vitro growth (IVG). Preantral follicles isolated from ovaries of Kunming mice were cultured in vitro. In the culture system, CNP was supplemented in the experimental groups and omitted in the control groups. In Experiment 1, CNP was only supplemented at the early stage and follicle development was evaluated. In Experiments 2 and 3, CNP was supplemented during the whole period of in vitro culture. In Experiment 2, follicle development and oocyte maturity were evaluated. In Experiment 3, follicle development and embryo cleavage after in vitro fertilization (IVF) were assessed. The results showed that in the control groups in all three experiments, granulosa cells migrated from within the follicle and the follicles could not reach the antral stage. In the experimental groups in all three experiments, no migration of granulosa cells was observed and follicle development was assessed as attaining the antral stage, which was significantly superior to that of the control group (P < 0.0001). Oocyte meiotic arrest was effectively maintained, hence giving good developmental competence. In conclusion, CNP supplementation in the culture system during IVG benefited the development of murine preantral follicles.

scholarly journals Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3975
Author(s):  
Marco A. De Velasco ◽  
Yurie Kura ◽  
Naomi Ando ◽  
Noriko Sako ◽  
Eri Banno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Late Stage ◽  
Early Stage ◽  
Castration Resistant Prostate Cancer ◽  
Akt Inhibitor ◽  
Molecular Features ◽  
Context Specific

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.

scholarly journals Comparative Evaluation of Fracture Resistance of Endodontically Treated Teeth Restored with Resin Fiber Post and Stainless Steel Post: An In Vitro Study

2015 ◽  
Vol 03 (02) ◽  
pp. 080-084
Author(s):  
Vijay Singh ◽  
Poonam Bogra ◽  
Saurabh Gupta ◽  
Navneet Kukreja ◽  
Neha Gupta
Keyword(s):  
Stainless Steel ◽  
Fracture Resistance ◽  
Testing Machine ◽  
Compressive Force ◽  
Control Group ◽  
Fiber Post ◽  
Endodontically Treated Teeth ◽  
Group I ◽  
Significant Difference

AbstractFracture resistance of endodontically treated teeth restored with post. Aims: This study aims to compare the fracture resistance of endodontically treated teeth restored with resin fiber and stainless steel post. Commercially available prefabricated resin fiber post(Dentsply Maillefer Easy Post), prefabricated stainless steel post(Coltene/Whaledent Parapost) were used. Methods and Material: Forty five maxillary central incisors were obturated and divided into 3 groups: Control Group (Group I) without any post (n = 15), Resin Fiber Post Group (Group II) (n = 15) and Stainless Steel Post Group (Group III) (n = 15). In all Groups except control group, post space was prepared; a post was cemented, and a core build-up was provided. All the specimens were subjected to compressive force under a universal testing machine until fracture. Statistical analysis used: The results were analyzed using the variable analysis test (ANOVA). Results: One-way analysis of variance revealed significant difference among test groups. The control group demonstrated highest fracture resistance (925.2183 N), followed by the resin fiber post group (486.7265 N) and stainless steel post group (423.539N). Conclusions: Teeth restored with resin fiber post showed higher fracture resistance values than prefabricated stainless steel post.

Should fertile women quit drinking alcohol to produce better quality oocytes?

Zygote ◽  
2020 ◽  
pp. 1-3
Author(s):  
Burcu Ozbakir ◽  
Pinar Tulay
Keyword(s):  
Alcohol Consumption ◽  
Young Women ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Control Group ◽  
Social Drinkers ◽  
Antral Follicles ◽  
Healthy Women ◽  
Significant Difference

Summary Alcohol consumption has long been shown to affect both fetal health and pregnancy. In this study, antral follicle count, maturation level of oocytes including morphological assessment and number of metaphase I (MI), metaphase II (MII) and germinal vesicle (GV) stage oocytes obtained from young women (age < 30 years old) with or without alcohol consumption were investigated. In total, 20 healthy women who were social drinkers and 36 healthy women who do not consume alcohol were involved in this study. Women in both study and control groups were undergoing controlled ovarian stimulation. The antral follicle count and the number and quality of the oocytes retrieved were evaluated and recorded. In total, 635 antral follicles, 1098 follicles and 1014 oocytes with 820 MII, 72 MI and 78 GV stage oocytes were collected from the social drinkers. In the control group, 628 antral follicles, 1136 follicles and 1085 oocytes with 838 MII, 93 MI and 102 GV stage oocytes were evaluated. The results of this study showed that the antral follicle count was very similar in both groups. The number of oocytes and MII stage oocytes was slightly higher in the control group, although it was not a significant difference. This study showed that although the consumption of alcohol may have adverse effects post-implantation, it may not have a solid effect during oogenesis in young women. The results of this study are especially important in clinical settings as some women who are social drinkers undergo in vitro fertilization treatments.

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