Intratracheal administration of p38α short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats

Lv, Xiangqi; Tan, Jing; Liu, Dongdong; Wu, Ping; Cui, Xiaoqian

doi:10.1016/j.healun.2012.03.001

Cited by 24 publications

(21 citation statements)

References 37 publications

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“…For instance, preservation advances can build on promising strategies that use perfusion circuits to mimic healthy physiological conditions 38,80,81 . These platforms can allow the organ to recover from cellular stress and tissue injury during donor death and organ procurement, which can contribute to inflammation and organ rejection following transplantation 80–83 , and also enable therapeutic intervention before transplantation 83–87 . The advent of ex vivo organ perfusion shows promise to make larger pools of donor organs available by enabling rehabilitation of organs that would otherwise be unsuitable for transplantation 38,41,82 .…”

Section: Organ Transplantation Without Preservation Constraintsmentioning

confidence: 99%

“…Any of several existing techniques might be part of the process to condition organs for transplantation or subsequent steps of the preservation process 83 ; these include drug-mediated immunomodulation to apply treatments that block or alter sites recognized by the recipient’s immune system to mitigate rejection 84,85 ; gene therapy 86,87 ; antisense, or RNA interference. Similar interventions could even be used to improve organs’ health and function, making them in some ways healthier in the recipient than they were in the donor.…”

Section: Organ Transplantation Without Preservation Constraintsmentioning

confidence: 99%

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The promise of organ and tissue preservation to transform medicine

et al. 2017

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The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

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Section: Organ Transplantation Without Preservation Constraintsmentioning

confidence: 99%

Section: Organ Transplantation Without Preservation Constraintsmentioning

confidence: 99%

The promise of organ and tissue preservation to transform medicine

et al. 2017

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“…Lung transplantation is the last-resort treatment option for patients with end-stage lung disease, but following lung transplantation, the patient 1-year survival rate is only ~70%; patients tend to succumb to post-operative mortality within 30 days of surgery (2). Graft failure following transplantation can cause lung I/R injury, including injury to the pulmonary vascular endothelium, resulting in marked lung damage (3).…”

Section: Introductionmentioning

confidence: 99%

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

Jin

Zhao

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Silymarin is a traditional therapeutic used to protect the liver, acting to oppose lipid peroxidation, to enhance liver regeneration and functioning as an antioxidant. However, the effects of silymarin on pulmonary vascular dysfunction have not been investigated. In the present study, the modulatory effects of silymarin on pulmonary vascular dysfunction and the underlying mechanisms behind this were investigated in a lung ischemia-reperfusion (I/R) injury rat model. Male Sprague Dawley rats were randomly divided into 3 groups, including: i) A control group (n=10); ii) an I/R group (n=10); and iii) a silymarin-treated group (n=10). All experimental rats received 250 mg/kg/day of silymarin for 8 days. Silymarin was demonstrated to markedly improve lung I/R-induced pulmonary vascular dysfunction and lung moisture. Following silymarin treatment, inflammation and oxidative stress in the lung I/R-injury rats were demonstrably suppressed. Treatment with silymarin also inhibited the activation of caspase-3 and -9, and hypoxia inducible factor-1α (HIF-1α) and inducible nitric oxide synthase (iNOS) protein expression in the lung I/R-injury rats. Silymarin was concluded to impact upon pulmonary vascular dysfunction through the HIF-1α-iNOS pathway in the lung I/R injury rat model.

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“…Amongst the studies discussed here, 15 ones used the i.t. route with [35, 67, 87] or without aerosolization [31, 37, 39, 42, 86, 89, 108, 119, 124, 134, 142, 143]. Another local and less invasive route for easily accessible administration of siRNA is the application of a nasal suspension in the nasal cavity.…”

Section: Administration Routementioning

confidence: 99%

siRNA Delivery to the lung: What's new?

Merkel

Rubinstein

Kissel

2014

Advanced Drug Delivery Reviews

116

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RNA interference (RNAi) has been thought of as the general answer to many unmet medical needs. After the first success stories, it soon became obvious that short interfering RNA (siRNA) is not suitable for systemic administration due to its poor pharmacokinetics. Therefore local administration routes have been adopted for more successful in vivo RNAi. This paper reviews nucleic acid modifications, nanocarrier chemistry, animal models used in successful pulmonary siRNA delivery, as well as clinical translation approaches. We summarize what has been published recently and conclude with the potential problems that may still hamper the efficient clinical application of RNAi in the lung.

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Intratracheal administration of p38α short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats

Cited by 24 publications

References 37 publications

The promise of organ and tissue preservation to transform medicine

The promise of organ and tissue preservation to transform medicine

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

siRNA Delivery to the lung: What's new?

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