IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

Xu, Liang; Zhang, Weijun; Liu, Jingquan; Hong, Jun; Li, Qian; Hu, Bangchuan; Gong, Fangxiao

doi:10.3892/etm.2017.4553

Cited by 15 publications

(12 citation statements)

References 34 publications

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“…IGF‐1R activation induces the downstream PI3K/Akt pathway, which can further activate mTOR or inactivate GSK‐3β. Sepsis‐induced inflammation has been shown to decrease IGF‐1 signalling pathway (Wasnik et al, 2020; Xu et al, 2017). Studies also found that sepsis or TNF‐related weak inducer of apoptosis (TWEAK), a member of the TNF ligand family, decreased Akt and GSK‐3β phosphorylation to induce skeletal muscle atrophy (Dogra et al, 2007; Li, Liu, & Wang, 2019).…”

Section: Discussionmentioning

confidence: 99%

Triptolide prevents LPS‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

Fang

Tseng

Lee

et al. 2021

British J Pharmacology

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Background and Purpose: Increasing evidence suggests systemic inflammationcaused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook F possesses potent anti-inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation-induced skeletal muscle atrophy. Experimental Approach: The effects of triptolide on skeletal muscle atrophy were investigated in LPS-treated C2C12 myotubes and C57BL/6 mice. Protein expressions and mRNA levels were analysed by western blot and qPCR, respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro-CT and grip strength, respectively. Locomotor activity was measured using the open field test. KEY RESULTS: Triptolide (10-100 fM) up-regulated protein synthesis signals (IGF-1/p-IGF-1R/IRS-1/p-Akt/p-mTOR) and down-regulated protein degradation signal atrogin-1 in C2C12 myotubes. In LPS (100 ngÁml À1 )-treated C2C12 myotubes, triptolide up-regulated MyHC, IGF-1, p-IGF-1R, IRS-1 and p-Akt. Triptolide also down-regulated ubiquitin-proteasome molecules (n-FoxO3a/atrogin-1/MuRF1), proteasome activity, autophagy-lysosomal molecules (LC3-II/LC3-I and Bnip3) and inflammatory mediators (NF-κB, Cox-2, NLRP3, IL-1β and TNF-α). However, AG1024, an IGF-1R inhibitor, suppressed triptolide-mediated effects on MyHC, myotube diameter, MuRF1 and p62 in LPS-treated C2C12 myotubes. In LPS (1 mgÁkg À1 , i.p.)-challenged mice, triptolide (5 and 20 μgÁkg À1 Áday À1 , i.p.) decreased plasma TNF-α levels and it increased skeletal muscle volume, cross-sectional area of myofibers, weights of the gastrocnemius and tibialis anterior muscles, forelimb grip strength and locomotion.Conclusions and Implications: These findings reveal that triptolide prevented LPS-induced inflammation and skeletal muscle atrophy and have implications for the discovery of novel agents for preventing muscle wasting.

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Section: Discussionmentioning

confidence: 99%

Triptolide prevents LPS‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

Fang

Tseng

Lee

et al. 2021

British J Pharmacology

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“…Both high and low UVR doses induced a transient up‐regulation of IGF‐1 expression in the ORS at day 1 after exposure (Figure a,c), which may be a compensatory response of the HF against UV‐induced oxidative stress . Long‐term effect (day 3 of organ culture) of UVR resulted in decreased expression of IGF‐1 expression in the HF epithelium but only upon irradiation with the high dose (Figure a,c).…”

Section: Resultsmentioning

confidence: 92%

Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine

Gherardini

Wegner

Chéret

et al. 2019

Intern J of Cosmetic Sci

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ObjectivesAlthough the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.MethodsHuman scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340–440 nm) + 20 mJ/cm2 UVB (290–320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organ‐cultured under serum‐free conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality read‐out parameters were measured in defined skin and HF compartments.ResultsConsistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVR‐mediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGF‐1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVR‐mediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential up‐regulation of the catagen‐promoting growth factor.ConclusionOur study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sun‐protective cosmeceutical and nutraceutical formulations.

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“…Evidence has also been presented of the antioxidant and antiinflammatory effects of IGF-1. It is assumed that its low levels may exacerbate oxidative stress injury in sepsis patients [93][94][95] Another hormone associated with the somatotropic axis is ghrelin. This is a relatively recently discovered hormone that acts on the GH secretagogues receptor (GHS-R) and stimulates the secretion of GH by the pituitary gland [96].…”

Section: Somatotropic Axismentioning

confidence: 99%

“…Evidence has also been presented of the antioxidant and anti-inflammatory effects of IGF-1. It is assumed that its low levels may exacerbate oxidative stress injury in sepsis patients [ 93 , 94 , 95 ]…”

Section: Endocrine Disorders In the Course Of Sepsismentioning

confidence: 99%

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

Wasyluk

Zwolak

2021

JCM

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Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

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IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

Cited by 15 publications

References 34 publications

Triptolide prevents LPS‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

Triptolide prevents LPS‐induced skeletal muscle atrophy via inhibiting NF‐κB/TNF‐α and regulating protein synthesis/degradation pathway

Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

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